Abnormalities of chromosome 16q in myeloid malignancy: 14 new cases and a review of the literature. Fourteen patients with abnormalities of chromosome 16q, 13 with acute myelogenous leukaemia (AML), and one with refractory anaemia with excess of blasts (RAEB), are described. Seven patients had inv(16)(p13q22), two had del(16)(q22), and five had other abnormalities of 16q. Six of the seven patients with inv(16) had AML M4Eo and, following treatment with adriamycin, cytosine arabinoside, and 6-thioguanine, all achieved complete remission (CR). Neither patient with del(16)(q22) had typical M4Eo morphology at diagnosis; CR was achieved in one and one had resistant leukaemia. Patients with other abnormalities of 16q had blasts of diverse morphology and, although morphologically abnormal eosinophils were seen in three patients, this was not as marked as in the patients with inv(16). CR was achieved in two of the four patients with other abnormalities of 16q but duration of remission was short in both cases. These results suggest that most patients with del(16)(q22) and other abnormalities of 16q22 do not have typical AML M4Eo. Such patients tend to have a worse prognosis, and are more likely to have complex karyotypes typical of secondary leukaemia.


The CD4 molecule belongs to the phenotypic repertoire of most cases of acute myeloid leukemia. In the present study fresh leukemic cells obtained from 23 patients with acute myeloid leukemia (AML; FAB subtypes: three M1, five M2, two M3, five M4, eight M5) were investigated for the membrane expression of the CD4 molecule by cytofluorimetric analysis with an anti-CD4 monoclonal antibody (mAb). In 15 cases the presence of the CD4 mRNA was also investigated using Northern blot analysis. Membrane expression of the CD4 molecule was demonstrated in 19 out of 23 cases, and it was found to be weaker than in CD4+ lymphocytes and monocytes obtained from normal controls. Full-length CD4 mRNA was detected in 12 out of 15 (80%) cases, and AML cells positive for CD4 mRNA expression also expressed the CD4 antigen. Since the CD4 molecule expressed by T cells is associated with p56lck, a member of the src family of intracellular tyrosine kinases, we investigated whether the CD4 molecule expressed by myeloid blasts is also associated with a tyrosine kinase activity. In vitro kinase assays performed on anti-CD4 immunoprecipitates from lysates of myeloid leukemia cells from four CD4+ cases were negative for the presence of a tyrosine kinase activity. This finding was not due to the lack of expression of members of the src family since we were able to detect at least p60src and p59fyn in myeloid leukemia cells. According to our results, the CD4 molecule seems to belong to the phenotypic repertoire of most AML, irrespective of their FAB subtypes. However, in myeloid blasts this molecule is not associated with a tyrosine kinase activity as it occurs in T lymphocytes.


Differences in the intracellular pharmacokinetics of cytosine arabinoside (AraC) between circulating leukemic blasts and normal mononuclear blood cells. The increasing insights into the pharmacokinetics and the metabolism of cytosine arabinoside (AraC) have improved the rationale for its application in leukemia therapy and have led to a pharmacologically directed design of antileukemic treatment. The current study aims at adding to this approach by detecting differences in the intracellular metabolism of AraC 5'-triphosphate (AraCTP) between leukemic and normal mononuclear blood cells. Measurements of intracellular AraCTP levels were complemented by determinations of plasma AraC and AraU concentrations and were performed in 32 patients with acute myeloid leukemia undergoing combination therapy including either conventional (100 mg/m2 daily) or high-dose (1.0 or 3.0 g/m2 twice daily) AraC. Plasma AraC concentration showed a linear relationship to the applied AraC dose but did not correlate with intracellular AraCTP levels. During conventional-dose AraC therapy little interpatient variation was observed in AraCTP retention times in leukemic blasts from 5 patients with t1/2 values ranging from 1.70 to 2.50 h (median 2.14 h). In all cases AraCTP levels declined rapidly after the end of the AraC infusion. Substantial differences in AraCTP retention times were revealed, however, during 3 h infusions of either 1.0 or 3.0 g/m2 AraC in leukemic blasts from 10 patients with t1/2 values between 1.60 to 7.63 h (median 2.42 h). In addition, AraCTP levels declined in only one patient by > 10% within the first hour after the end of therapy and remained constant or even increased up to 1.5-fold in a post-treatment period of 1 to 2.5 h in the other nine cases. In contrast, AraCTP retention times were relatively uniform in normal mononuclear blood cells from 11 patients with t1/2 values of 3.34 to 5.29 h (median 3.85 h). More importantly, AraCTP levels dropped by > 10% within the first hour after the end of the high-dose AraC infusion in eight of 11 cases. A post-therapeutic increase > 10% was not observed in any patient. Similar findings emerged after in vitro exposure of normal bone marrow cells from six healthy volunteers to 20 mumol/l AraC for 3 h revealing a > 10% decrease of intracellular AraCTP within the first post-treatment hour in all cases with AraCTP retention times of 2.29 to 8.63 h (median 3.20 h). These differences in AraCTP pharmacokinetics between leukemic and normal blood cells may provide the basis for a modified timing of AraC administration with the aim of selectively maintaining cytotoxic AraCTP levels in leukemic blasts while allowing an intermittent drop of AraCTP levels in normal cells.(ABSTRACT TRUNCATED AT 400 WORDS)


A retinoid acid 'resistant' t(15;17) acute promyelocytic leukemia cell line: isolation, morphological, immunological, and molecular features. We report the isolation of a maturation-resistant acute promyelocytic leukemia (APL) cell line. This permanent cell line, derived from the same patient as the maturation inducible NB4 cell line, is the first retinoid-resistant cell line with a t(15;17) chromosomal translocation. Morphological, immunocytochemical and molecular features of the maturation responsive (NB4) and unresponsive (NB4-RAr) cells are compared. The isolation of the NB4-RAr cell line occurred through a two-step process requiring the continuous selective pressure of all-trans-retinoic acid. Cells are also resistant to 13-cis-retinoic acid. Karyotypic and Southern-blot analyses show that the two cell lines are similar with respect to the translocation. Northern-blot analyses show that the chimeric fusion transcript PML-RAR alpha and the normal allelic PML and RAR alpha transcripts are similarly expressed in both cell lines. The molecular basis for unresponsiveness to retinoic acid is not known. This resistant cell line offers a cellular model for molecular biology studies on the mechanism of induction of APL cell maturation, as well as a means to elucidate the molecular mechanisms of resistance. It also furnishes a unique tool for designing and/or screening new therapeutic drugs to avoid or relieve retinoid maturation blockage.


Absence of negative growth regulation in three new murine radiation-induced myeloid leukemia cell lines with deletion of chromosome 2. Murine radiation-induced acute myeloid leukemia (RI-AML) may be considered as the experimental counterpart of human secondary leukemia. Three new myelomonocytic cell lines derived from RI-AML and carrying a partially deleted chromosome 2 are described. The RI-AML cells responded with increased proliferation after being incubated with the hemopoietic growth factors rG-CSF, rGM-CSF and IL-3. Increased proliferation of the same extent without any effect in differentiation, was also demonstrated in the RI-AML cells after incubation with IL-6 and with mouse lung conditioned medium (CM) and Krebs ascites tumor cells CM which induce differentiation in normal and most leukemic myeloid cells. Down-regulation of the c-myc gene and induction of (2'-5') oligo-adenylate synthetase (reflecting autocrine interferon secretion), two essential mechanisms operating during arrest of growth and concomitant differentiation, were demonstrated to be absent in RI-AML cells. In contrast, the M1 cells responded to the above differentiating factors with growth arrest and differentiation and with appropriate c-myc down-regulation and synthetase induction. The genetic basis for the distinct RI-AML cells' behavior may be connected with the loss or structural and/or functional abnormalities of DNA sequences located in the deleted part of chromosome 2 or in the respective allele. The presently described new RI-AML cell lines may be used for studies concerning myeloid leukemogenesis in general and secondary leukemia in particular.


P53 mutations in myelodysplastic syndromes. Point mutations in the p53 tumor-suppressor gene are the most frequently identified genetic alterations in human malignancies. In order to evaluate the role of p53 mutations in the multistep process of leukemogenesis we studied 61 patients with myelodysplastic syndromes using single-strand conformation polymorphism analysis of polymerase chain reaction products as well as direct sequencing. Mutant alleles were observed in 1/14 refractory anemia with excess of blasts (RAEB) and 2/5 RAEB in transformation. The three mutations represented G:C to A:T transitions at codon 141 (exon 5) and codons 245 and 248 (exon 7), respectively. These data suggest that p53 mutations may contribute, albeit rarely, to the development of preleukemic disorders of the myeloid cell lineage.


The need for standards in recording and analysing respiratory sounds. Respiratory sounds (RSs) recorded from the chest and trachea are nowadays being electronically analysed by many investigators with a view to (i) determining the mechanisms of their production, and (ii) to develop automated diagnostic systems based on RS analysis, that objectively categorise RS as being associated with health or respiratory diseases. However, one problem that hampers this type of research is that almost every RS investigation team uses different equipment, protocols and analysis methods which, to varying degrees, makes inter-investigator results difficult to compare. The review first discusses the many variables involved in RS recording and analysis, and the different approaches used by different investigators, to highlight this problem and its consequences. Secondly, although the review cannot propose immediately acceptable guidelines and standards for RS analysis, it proposes a 'seed' set of guidelines that are 'up for discussion' between investigators in the field, the final goal being to inject a degree of standardisation in equipment and methods that are acceptable to all involved.


Impedance changes during the compound nerve action potential: implications for impedance imaging of neuronal depolarisation in the brain. Impedance changes were measured during the compound action potential (CAP) in isolated crab nerves with 50 kHz or direct applied current (DC), to suggest an optimal frequency for the imaging of neuronal depolarisation by electrical impedance tomography (EIT). With DC, a predominant apparent impedance decrease of 0.2-0.7 per cent of the resting baseline was observed, which had a time course similar to that of the action potential. Control recordings suggested that these changes could not be attributed to technical errors resulting from the measurement method. A component in some measurements was attributable to effects of the measuring current on the latency of the CAP, but the mechanism underlying the remainder of the changes was unclear. No changes greater than +/- 0.005 per cent were seen with measurement at 50 kHz. This suggests that research into noninvasive rapid imaging of nervous activity in the brain with EIT would be more profitably performed with measurements at frequencies lower than the 50 kHz currently used for safety reasons.


Noninvasive acoustical detection of coronary artery disease using the adaptive line enhancer method. Previous studies have indicated that heart sounds may contain information which is useful in the detection of occluded coronary arteries. Specifically, previous work based on analysing heart sounds recorded during the diastolic portion of the cardiac cycle, when blood flow through the coronary arteries is maximum, has shown that additional frequency components are present in patients with coronary artery disease. To further explore the application of advanced signal processing techniques to the noninvasive detection of coronary artery disease, a new signal-processing approach is presented using adaptive line enhancing (ALE) and spectral estimation of diastolic heart sounds taken from recordings made at the patient's bedside. This approach comprises two cascaded processes. In the first the ALE method is used to enhance the diastolic heart sounds and eliminate background noise. In the second process, either autoregressive (AR) or autoregressive moving average (ARMA) spectral methods are used to estimate the model parameters. Model parameters (the power spectral density (PSD) functions and the poles of the AR or ARMA method) were used to diagnose patients as diseased or normal. Results showed that normal and abnormal recordings were correctly identified in 39 of 43 cases using the new method. These results also confirm that high-frequency energy above 400 Hz is associated with coronary stenosis.


Heart rate and body temperature sensitive diaphragm pacing. Two ways of rate control for diaphragm pacing are proposed. One is rate control using only the patients' body temperature (method I). The other is rate control by both the patients' heart rate and body temperature (method II). To test the effectiveness of these methods, a diaphragm pacemaker which can be controlled by both heart rate and body temperature has been developed. It was applied to nine mongrel dogs. The pacing rate is controlled by atrial blood temperature (method I) or by both heart rate and temperature (method II). The animal's metabolism was elevated by the administration of a pyrogenic drug. It was found that method I is not suited to rapid changes in metabolism; however, it is useful in extreme metabolic elevation. An animal's metabolism was supported by using method II in all ranges of metabolism. This method proved more effective than method I for rate-responsive diaphragm pacing.


Closed-chest cardiac stimulation with a pulsed magnetic field. Magnetic stimulators, used medically, generate intense rapidly changing magnetic fields, capable of stimulating nerves. Advanced magnetic resonance imaging systems employ stronger and more rapidly changing gradient fields than those used previously. The risk of provoking cardiac arrhythmias by these new devices is of concern. In the paper, the threshold for cardiac stimulation by an externally-applied magnetic field is determined for 11 anaesthetised dogs. Two coplanar coils provide the pulsed magnetic field. An average energy of approximately 12 kJ is required to achieve closed-chest magnetically induced ectopic beats in the 17-26 kg dogs. The mean peak induced electric field for threshold stimulation is 213 V m-1 for a 571 microseconds damped sine wave pulse. Accounting for waveform efficacy and extrapolating to long-duration pulses, a threshold induced electric field strength of approximately 30 V m-1 for the rectangular pulse is predicted. It is now possible to establish the margin of safety for devices that use pulsed magnetic fields and to design therapeutic devices employing magnetic fields to stimulate the heart.


Component wave delineation of ECG by filtering in the Fourier domain. A complete solution to the fundamental problem of delineation of an ECG signal into its component waves by filtering the discrete Fourier transform of the signal is presented. The set of samples in a component wave is transformed into a complex sequence with a distinct frequency band. The filter characteristics are determined from the time signal itself. Multiplication of the transformed signal with a complex sinusoidal function allows the use of a bank of low-pass filters for the delineation of all component waves. Data from about 300 beats have been analysed and the results are highly satisfactory both qualitatively and quantitatively.


The effect of averaging cardiac Doppler spectrograms on the reduction of their amplitude variability. The effect of averaging cardiac Doppler spectrograms on the reduction of their amplitude variability was investigated in 30 patients. Beat-to-beat variations in the amplitude of Doppler spectrograms were also analysed. The quantification of amplitude variability was based on the computation of the area under the absolute value of the derivative function of each spectrum composing mean spectrograms. Fast Fourier transform using a Hanning window was used to compute Doppler spectra. Results obtained over systolic and diastolic periods showed that the reduction of amplitude variability followed an exponentially decreasing curve characterised by the equation f (r) = 100 e-beta(r-1), where r is the number of cardiac cycles, beta the exponentially decreasing rate, and 100 the normalised variability for r = 1. In systole, the decreasing rate beta was 0.165, whereas in diastole it was 0.225. Reductions of the variability in systole for a number of cardiac cycles of 5, 10, 15, and 20 were 48, 77, 90 and 96 per cent, respectively. In diastole, reductions of the variability for the same numbers of cardiac cycles were 59, 87, 96 and 99 per cent, respectively. Based on these results, it can be concluded that no significant improvement in the reduction of amplitude variability may be obtained by averaging more than 20 cardiac cycles.


Six-band sub-band coder on ECG waveforms. An ECG sampled at a rate of 500 samples s-1 or more produces a large amount of redundant data that are difficult to store and transmit. A process is therefore required to represent the signals with clinically acceptable fidelity and with the least code bits possible. In the paper, an efficient sub-band coding method for encoding ECG waveforms is presented. Although sub-band coding has been successfully applied to speech signals, it is the first time that this technique has been applied to the encoding of ECG waveforms. A frequency band decomposition of an ECG waveform is carried out by means of quadrature mirror filters (QMF), which split the ECG spectrum into six bands of unequal width. In the lower frequency bands, which contain most of the ECG spectrum energy, a larger number of bits per sample is used, whereas in upper frequency bands, which contain noise-like signals, fewer bits per sample and the run length coding method are used. The simulation results are presented in terms of bit rates and the quality of the reconstructed waveforms. The results show that a reproduction with an average signal-to-noise ratio (SNR) of 29.97 dB can be achieved even at an average bit rate of 0.81 bits per sample.


Comparison between the more recent techniques for smoothing and derivative assessment in biomechanics. When analysing and evaluating human motion, two strictly interconnected problems arise: the data smoothing and the determination of velocities and accelerations from displacement data. Differentiating procedures magnify the noise superimposed on the useful kinematic data. A smoothing procedure is thus required to reduce the measurement noise before the differentiation can be carried out. In the paper two techniques for derivative assessment are presented, tested and compared. One of these is the procedure known as one of the best automatic smoothing and differentiating techniques: generalised cross validatory spline smoothing and differentiation (GCVC). The other, which has recently been presented, features an automatic model-based bandwidth-selection procedure (LAMBDA). The procedures have been tested with signals presented by other authors and available in the literature, by test signals acquired using the ELITE motion analyser and by synthetic data. The results show better or similar performance of LAMBDA compared with GCVC. In the cases in which the natural conditions at the signal boundaries are not met GCVC gives bad results (especially on the third derivative) whereas LAMBDA is not affected at all. Moreover, analysis time is dramatically lower for LAMBDA.


On/off control in FES-induced standing up: a model study and experiments. Control of paraplegic standing up was studied with respect to the limitation of the end-velocity of the knee joint when the patient reaches the upright position. Closed-loop on/off control of knee extensor muscle was compared with open-loop controlled standing up both in a model study and in paraplegic patients in a controlled model situation. Criteria were knee-end-velocity and knee extensor muscle activation time. Sensitivity of the system to additional arm support and (in the model study) to the dynamics of knee extensor muscle was studied. It is concluded that the control scheme may reduce knee-end velocity to about 40 per cent and knee extensor activation time to near 70 per cent of the respective open-loop values.


FFT-based digital tactile vocoder system for real-time use. A microprocessor-based real-time digital vibrotactile vocoder system has been developed to train the deaf and for artificial hearing research. The system is composed of a microcomputer module with a digital signal processor, interface units and an attenuator/driver circuit. Live or digitised (stored or synthetic) speech is presented to the skin spectrally through a belt housing eight or 16 vibrators. Speech is processed in real time using a fast Fourier transform. The system is also capable of presenting any arbitrary spatiotemporal pattern on the skin for artificial hearing experiments. A preliminary experiment with a deaf subject indicates that the system is potentially an effective device for artificial hearing.


Vectorial measurement of blood velocity by means of ultrasound. The complete determination of blood velocity as a vector can be achieved using ultrasound techniques, by correlating the echo signals provided by a sector transducer. Here the general problem is approached by suggesting the processing procedure which should be adopted, so that longitudinal and transverse velocity components can be separated. After this a specific transducer layout is considered, which is suitable for in-plane measurements, and possible performances are evaluated by means of simulation. Finally, an experimental facility, set up to demonstrate the validity of the theoretical lines developed in two-dimensional geometry, is described, together with the preliminary results obtained.


Treatment of chronic wounds by means of electric and electromagnetic fields. Part 1. Literature review. The healing of a cutaneous wound is accompanied by endogeneous electrical phenomena. Not knowing whether they represent merely a side-effect of the physiological processes which take course during healing or whether they play a much more important role as mediators of healing, externally applied electricity was examined as a therapeutic tool for the enhancement of natural regenerative processes. In the present review a historical literature survey dealing with human applications of electric current for wound healing acceleration is given. It presents a complete palette of heterogeneous studies, differing in the parameters of applied electric current, in delivery modes as well as in the types of wounds being stimulated. Because of all these differences, comparing the efficacy of the described methods is difficult and could hardly be objective. Therefore greater stress was laid upon the discussion concerning the problems in designing clinical studies (size of the sample observed, control group, ethics of the procedures), rationales for the employment and possible underlying mechanisms of particular methods, and problems of evaluating their efficacy. In spite of the extensive work performed in the field of electrical wound healing we remain only part way towards explaining the mechanisms by which electricity reinforces the regenerative capabilities of injured tissue as well as only part way towards the selection of the optimal stimulation method from among the published reports.


Effect of ensemble averaging on amplitude and feature variabilities of Doppler spectrograms recorded in the lower limb arteries. The objective of the present study was to analyse the effect of averaging Doppler blood flow signals in lower limb arteries on amplitude and feature variabilities. Doppler signals recorded in 41 iliac and 35 superficial femoral arteries having different categories of stenosis were averaged over 1-15 cardiac cycles. Based on the relative decreasing rate of an index of variability, results indicated that amplitude variability of the spectrograms was exponentially reduced to 30, 6 and 1 per cent when averaging five, ten and 15 cardiac cycles, respectively. Nine diagnostic features were extracted from Doppler spectrograms and their variations from one cardiac cycle to the next quantified. Based on the relative decreasing rate of these variations, results indicated that feature variability was exponentially reduced to 30, 4 and 1 per cent when averaging five, ten and 15 cardiac cycles, respectively. The effect of averaging on the discriminant power of the features to separate the different categories of stenosis was also investigated by performing t-test analyses. Results showed that averaging between five and ten cardiac cycles provided the better discriminant power for most cases, whereas averaging over more than ten cardiac cycles was of little benefit. Based on the spectral analysis technique used in the present study, we conclude that averaging over ten cardiac cycles is sufficient for the analysis of Doppler spectrograms recorded in the lower limbs.


Frequency domain analysis of highly amplified ECG on the basis of maximum entropy spectral estimation. Recognition of patients with high risk for ventricular tachycardia (VT) or sudden cardiac death is of high clinical importance. We have investigated the efficiency of maximum entropy spectral estimation (MES) to detect such risk patients on the basis of highly amplified surface ECG. In comparison with the traditionally applied periodogram (fast Fourier transform), the MES produces sharper and more pronounced peaks in the power density spectrum (PS). The main problem is the influence of residual noise (after averaging), which often leads to additional components in the PS. To completely avoid this negative noise influence we developed a new algorithm, called the variance subtraction method. In a first clinical investigation 86 per cent of patients with myocardial infarction and ventricular tachycardia have shown frequency components above 80 Hz in the PS compared with healthy persons where no frequency components above this 80 Hz level could be detected.


Duchenne muscular dystrophy quantification: a multivariate analysis of surface EMG. The paper describes a method of quantifying Duchenne muscular dystrophy which is examiner independent and uses surface electromyographic signals (EMG). A standardised protocol is proposed. Spectral parameters are first computed from digitised EMG, then a polynomial model is deduced from the evolution of each parameter. A discriminant analysis between healthy and DMD subjects leads to the determination of a discriminant plane and a level of sickness index.


Propagation model using the DiFrancesco-Noble equations. Comparison to reported experimental results. Propagation, re-entry and the effects of stimuli within the conduction system can be studied effectively with computer models when the pertinent membrane properties can be represented accurately in mathematical form. To date, no membrane models have been shown to be accurate representations during repolarisation and recovery of excitability, although for the Purkinje membrane the DiFrancesco-Noble (DN) model has become a possibility. The paper examines the DN model, restates its equations and compares simulated waveforms in a number of propagation contexts to experimental measurements reported in the literature. The objective is to determine whether or not the DN model reproduced phenomena such as supernormality, shortening in action potential duration during pacing rate increases, alternation of duration with changes in rhythm, graded responses and 'all-or-none' repolarisation in a quantitatively realistic way, as each of these come from time and space dependencies not directly a part of the ionic current measurements on which the DN model is based. The results show that the DN equations correctly simulate these situations and support the goal of having a model that is broadly applicable to Purkinje tissue, including refractory period properties and response to electrical stimulation.


Potential distribution and single-fibre action potentials in a radially bounded muscle model. In modelling the electrical behaviour of muscle tissue, we used to employ a frequency-dependent volume conductor network model, which was infinitely extended in all directions. Equations in this model could be solved using a finite-difference approach. The most important restriction of this model was the fact that no boundary effects could be incorporated. Analytical models of muscle tissue normally do not have this disadvantage, but in those models the microscopic structure of muscle tissue cannot be taken into account. In the paper, we present a combined numerical/analytical approach, which enables the study of potential distributions and SFAPs in simulated microscopic muscle tissue in which the influence of the muscle boundary has been considered. We considered muscle models with radii of 1.5 mm and 10 mm. Both models were compared with an unbounded network model. In the model with a radius of 1.5 mm we varied the position of the active fibre relative to the muscle surface. It appeared that in most cases the presence of a boundary had a considerable effect on the potential distribution. An increase in the peak-to-peak value of the SFAP amplitude up to 300 per cent was noticed when the active fibre was positioned 500 microns beneath the muscle surface in a model with a radius of 1.5 mm.


Mathematical modelling of flow distribution in the human cardiovascular system. The paper presents a detailed model of the entire human cardiovascular system which aims to study the changes in flow distribution caused by external stimuli, changes in internal parameters, or other factors. The arterial-venous network is represented by 325 interconnected elastic segments. The mathematical description of each segment is based on equations of hydrodynamics and those of stress/strain relationships in elastic materials. Appropriate input functions provide for the pumping of blood by the heart through the system. The analysis employs the finite-element technique which can accommodate any prescribed boundary conditions. Values of model parameters are from available data on physical and rheological properties of blood and blood vessels. As a representative example, simulation results on changes in flow distribution with changes in the elastic properties of blood vessels are discussed. They indicate that the errors in the calculated overall flow rates are not significant even in the extreme case of arteries and veins behaving as rigid tubes.


Cardiovascular responses to external counterpulsation: a computer simulation. A mathematical model of the human cardiovascular system is presented which includes a simulation of cardiac assistance by external counterpulsation. The model was established to study the effects of external counterpulsation on cardiovascular haemodynamics. The closed simulation includes both the left and the right heart and the pulmonary circulation. The model is able to provide data for the behaviour of the system under varying modes of assistance. Our results suggest that control of external counterpulsation is more difficult than control of the intra-aortic balloon pump and requires regulation of a larger number of variables. The results also suggest that a tradeoff exists between improved oxygen delivery to the heart and reduction in the oxygen consumption of the myocardium, an observation similar to that reported for the intra-aortic balloon pump.


Equivalent dipole estimation of spontaneous EEG alpha activity: two-moving dipole approach. A method of estimating equivalent moving and fixed dipoles from the scalp-recorded EEG alpha waves, with the realistic geometry of the head taken into account, is presented. Twenty-one silver electrodes were used to collect spontaneous EEG alpha waves on the scale. Four models, the single-moving dipole model, the single-fixed dipole model, the two-moving dipole model and the two-fixed dipole model were applied to approximate the EEG alpha field on the scalp. The algorithm, based on a least-squares fit for estimating the moving and the fixed dipoles by using a realistically shaped head model, is described. The numerical accuracy of the algorithm is also evaluated by a computer simulation. It is found that the spontaneous EEG alpha activity observed on the scalp can be represented by two equivalent moving dipoles, simultaneously located separately in the occipital regions of the right and the left hemisphere, at a depth of 4-6 cm beneath the scalp, with a goodness-of-fit of up to 97 per cent for all subjects examined. The excellent fit of the two-moving dipole model to the EEG human alpha activity is also compared with the single-dipole fit.


Droop: a rapidly computable descriptor of local minimum tissue temperature during conductive interstitial hyperthermia. Although the goal of local hyperthermia therapy for cancer is to elevate the temperature of a tumour to cytotoxic levels, without the presence of 'cold spots', varying blood flow has made the achievement of consistent, therapeutic temperature distributions extraordinarily difficult. The paper presents a novel approach to estimating local minimum tumour temperatures during conductive interstitial hyperthermia which facilitates identification and elimination of cold spots. Conductive interstitial hyperthermia is modelled mathematically for a parallel array of implanted, electrically heated catheters which warms the treated tissue by thermal conduction and blood perfusion. Computer simulations employing the bioheat transfer equation reveal a predictive relationship between implanted catheter temperature, catheter power, implantation geometry and local minimum tumour temperature. Formulation of this relationship in terms of a parameter named 'droop' allows estimation of local minimum intratumoural temperatures from individual catheter temperature and power. Computer simulations are also performed to determine the sensitivity of the droop-based estimator to variations in properties of the tissue and catheters. Generally, variations in geometry or thermal properties of about 10 per cent cause estimation errors of less than 1 degree C in magnitude. These results suggest that online estimates of thermal 'droop' may provide a practical route to more consistent control of intratumoural minimum temperature during conductive interstitial heat therapy.


Semiautomatic three-dimensional knee motion assessment system. A semiautomatic three-dimensional knee motion assessment system has been developed based on an optoelectric motion tracking system connected to an IBM-compatible computer. Critical decisions made in implementing the software component of the system include the modelling of the thigh and lower leg segments, calculating the knee angles, reaction forces, and moments; the file structure used and the format of the programs used to process the data are outlined. Once the subject-specific data have been collected, the system of programs requires no other user-intervention during processing. Also, selected curve parameters are automatically extracted from the output and combined with the subject-specific data that include precision X-ray and anthropometric data, which are all added to a knee motion assessment database. The automated portion of the system frees the experimenter from data processing and allows concentration on data analysis.


Approach to the estimation of alveolar pressure from noninvasive measurement of upper airway resistance. An alternative to whole body plethysmography is proposed for estimating upper airway resistance. The feasibility study indicates that the method should be suitable for diagnostic and clinical purposes, following a proper survey and the testing of its reproducibility. 11 subjects are asked to breath normally through 12 small resistances while flow and pressure are monitored at the mouth. Chest movements are recorded by sampling a chest cross-section, and relative variations of the cross-section are compared to the expired and inspired volumes. No viscoelastic effects are significantly documented so that in a first approximation a model consisting only of resistors is applied to the airways. In each subject the patterns of the flow and mouth-pressure are heuristically estimated as a polynomial function of the added resistance. From the fit of the resistor model, the internal resistance of the airways is estimated as that value able to link the flow-resistance function to the pressure-resistance function, according to the classic Kirchhoff laws. We obtain resistances of (mean resistance +/- SD) 2.9 +/- 1.1, range 1.1 to 5.2, hPasdm-3 during expiration and 2.5 +/- 0.8, range 1.3 to 3.7, hPasdm-3 during inspiration.


Radial changes of extracellular potential amplitude and integral characteristics and the inverse problem in electroneurography. The possibility of solving the inverse problem in electroneurography, i.e. of estimating the main parameters specifying the activated fibre's functional state, using the amplitude and integral characteristics of the surface potentials generated by infinite homogeneous fibres, has been analysed. An analytical expression has been found for the amplitude of the negative phase Anph of the single fibre extracellular action potential (SFEAP) as a function of the wavelength b, the fibre-electrode distance y and a scale factor Ao proportional to the intracellular action potential amplitude Vm, to the square of the fibre radius a and to the ratio of the axoplasm conductivity sigma a and volume conductor conductivity sigma e. For a large fibre-electrode distance, typical of surface recordings, an analytical expression of the integral of the negative phase Inph of the SFEAP as a function of Ao, b, y and the propagation velocity v was also found. Simple methods are proposed for estimating v, the location of the electrical centre of the activated fibres' territory and the product of the number of activated fibres N, duration T(in) of the intracellular action potential and of the factor Ao. The estimation errors due to the temporal and spatial dispersion of the activated fibres were analysed as a function of the fibre-electrode distance and the territory shape.


Effect of the Clinical Laboratory Improvement Amendments of 1988 (CLIA '88) on the incidence of invasive cervical cancer. The Clinical Laboratory Improvement Act of 1988 (CLIA '88) mandates strict, new quality-control measures for laboratories that interpret cervical cytology smears. Proposed regulations include proficiency testing of cytotechnologists and remediation for technologists and laboratories that fail to meet proposed proficiency standards. Proponents of the new regulations argue that these measures will reduce deaths from cervical cancer by reducing the false-negative rate of the Papanicolaou (Pap) test, but opponents argue that the regulations will increase the price of processing Pap tests and thereby reduce access to cervical cancer screening for high-risk, vulnerable populations. To examine these claims the authors used David Eddy's published simulation to model the natural history and detection of cervical neoplasia, and developed a new model to examine the health consequences of diminished access to Pap testing. The authors estimated the false-negative rate of the Pap test and the price elasticity of demand for preventive services on the basis of the published literature, and modeled the entire range of published or quoted predictions about the impact of CLIA '88 on accuracy and price. The results show that, if effects on access are ignored, reducing the false-negative rate from 15% to 5% would prevent 66 invasive cancers per 100,000 average risk women screened. However, under moderate assumptions regarding the effect of price on access, the regulations would prevent only 11 (instead of 66) cancers per 100,000 eligible women. The regulatory effect is very sensitive to the degree of improvement in the false-negative rate and increase in price that the regulations cause. Over the range of assumptions and predictions encountered in the literature and tested in our analysis, the proposed regulations could greatly reduce or greatly increase the incidence of invasive cancer, especially among high-risk and uninsured women. The implementation of the regulations should be delayed until new information regarding the actual false-negative rate of the Pap test allow a more precise estimate of the potential impact on the incidence of cervical cancer.


Variation in a medical faculty's decisions to transfuse. Implications for modifying blood product utilization. Previous studies have identified disconcerting differences in transfusion practices among physicians. This article investigates decisionmaking on transfusion by a medical school faculty. One hundred fourteen physicians indicated their propensity to transfuse 24 hypothetical patients who varied systematically in four clinical cues. Physicians agreed with transfusion for a widely divergent number of these patients (mean, 14.6; standard deviation, 5.5; range, 0 to 24). Although the physicians agreed on the order of importance of the clinical cues, they varied significantly in the importance they empirically attributed to the cues and in their thresholds for transfusion. Aside from a slightly higher propensity to transfuse by general internists, differences in decisionmaking were not attributable to physician-based variables. The wide variability in decisionmaking among physicians in the face of agreement on the order of importance of clinical cues suggests that quality assurance programs, and guidelines that only list the cues that ought to influence transfusion decisions, have low potential to achieve blood-product conservation.


A discrete choice model of alcoholism treatment location. In this study, a discrete choice model of alcoholism treatment location, with special emphasis on the roles of comorbidities is considered. Three specific questions are addressed: 1) what demographic and health factors have significant impacts on treatment location for both short- and long-term alcoholism and nonalcoholism treatments?; 2) how does the impact of alcohol dependence differ from the impact of alcohol abuse, on probabilities of short-term or long-term inpatient treatment?; and 3) what are the impacts of health comorbidities on probabilities of inpatient treatment in the short or long term? A binomial logit model is estimated for short- and long-term alcoholism treatment, as well as for short- and long-term nonalcoholism treatment (which occurs at the same time). The results indicate the importance of comorbidities in predicting treatment location. They also indicate a trend during the 1980s toward increased use of outpatient rather than inpatient treatment.


Development of the 'Activities of Daily Vision Scale'. A measure of visual functional status. To develop a method for the evaluation of visual function in subjects with cataracts, the authors identified 20 visual activities and categorized them into five subscales (distance vision, near vision, glare disability, night driving, and daytime driving) that comprised the Activities of Daily Vision Scale (ADVS). Each subscale in the ADVS was scored between 100 (no visual difficulty) and 0 (inability to perform the activity because of visual difficulty). In 334 subjects scheduled for cataract extraction (mean age 75 +/- 9 years, 67% women), ADVS scores (mean +/- standard deviation) for each subscale ranged from 44 +/- 31 for night driving to 72 +/- 24 for near vision activities. When administered by telephone, inter-rater reliability coefficients (r) were 0.82 to 0.97 (P < 0.001) for each of the subscales, and test-retest reliability was 0.87 for the scale overall. Cronbach's coefficient alpha was very high for both the in-person (alpha = 0.94) and telephone (alpha = 0.91) formats. Criterion validity, the correlation between visual loss and ADVS score, was -0.37 (P < 0.001) when the ADVS was administered in person and -0.39 (P < 0.001) when it was administered by telephone. Content validity as assessed with factor analysis showed that 88% of the variance of the principal components weighted on one factor. The authors conclude that substantial visual disability is not captured by routine visual testing and that the ADVS is a reliable and valid measure of patient's perception of visual functional impairment.


Development and validation of the Nursing Severity Index. A new method for measuring severity of illness using nursing diagnoses. Nurses of University Hospitals of Cleveland. The purpose of this study was to develop and validate the Nursing Severity Index, a new method used to measure the admission severity of illness of hospital patients using nursing diagnoses, which categorize biologic, functional, cognitive, and psychosocial abnormalities. This retrospective cohort study with independent development and testing phases was conducted at a U.S. academic medical center. In the development phase, data regarding 14,183 adult medical-surgical patients admitted to the medical center in 1985 and 1986 was used. In the testing phase, data regarding 7,302 patients admitted in 1987 and 1988 was used. Primary nurses prospectively recorded the presence or absence of 61 nursing diagnoses on admission. Demographic and clinical data were obtained from hospital data bases. In the development phase, the number of admission nursing diagnoses was highly related (P < 0.001) to in-hospital mortality. Using multiple logistic regression, 34 nursing diagnoses were identified as independent predictors of mortality; the Nursing Severity Index equals the number of these 34 diagnoses. In the testing phase of 7,302 patients, the Nursing Severity Index was related (P < 0.001) to mortality rates, which were 0.5%, 1%, 2%, 6%, 13%, 22%, and 31% in seven hierarchical strata defined by the Index. The Index was as accurate in predicting mortality as MedisGroups (receiver-operating-characteristic curve areas, 0.814 +/- 0.016 vs. 0.845 +/- 0.015, respectively, P = 0.12). Furthermore, the Nursing Severity Index and MedisGroups together (receiver operating characteristic curve area 0.880 +/- 0.014), were more accurate (P < 0.01) than either measure alone. The Nursing Severity Index assesses multiple dimensions of illness, can be easily measured during routine patient care, accurately predicts the risk of in-hospital death, and has similar prognostic accuracy as MedisGroups. Its usefulness in outcomes assessment, quality assurance, and case management merits further study.


A receiver operating characteristic (ROC) curve analysis of a model of mental health services use by Puerto Rican poor. In this study, the contribution of four distinct domains of the Help Seeking-Decision Making model to predicting the use of mental health services is examined. Using a proposed methodology the authors assess the relevance of this model and its domains to mental services planning. The methodology combines logistic regression analysis and receiver operating characteristic (ROC) curves. Logistic regression analysis allows us to examine the individual variables of the model and generate predictions about use. ROC curves allow us to compare and interpret the relative contribution of a predisposing domain, a physical and mental health domain, an enabling-restrictive domain, and an organizational domain in correctly classifying users and nonusers of mental health services. The physical and mental health domain yielded a Somer's D-statistic of 0.7, which corresponds to an 85% correct classification of randomly selected pairs of users and nonusers. The study findings suggest that comparing ROC curves helps to describe and interpret the domains of the model that are relevant for making predictions about who will or will not use mental health services during a 1-year period.


[Parotiditis in postvaccination period. Epidemiologic pattern and vaccine effectiveness in an epidemic outbreak]. Upon the detection of an excess number of cases of parotiditis in La Almolda (Zaragoza) a descriptive study of the epidemic was carried out with vaccination efficacy being quantified. The definition and system of detection of the cases was established. To calculate the rate of infection the available demographic data were used as denominators. A study of retrospective groups was designed to calculate the vaccination efficacy including one group of vaccinated subjects and another of non vaccinated subjects. Age and viral contact were considered as inclusion criteria. Fifty-two cases of parotiditis were detected. The rate of infection in a population of under 30 years of age was 18.9%. The most affected age group corresponded to the interval of between 10-14 years of age with a specific rate of 46.5%. The risk of infection was greatest amongst public school students (RR = 5; p = 0.00015). Vaccination efficacy was 74.68%. This study confirms the tendency that parotiditis affects older subjects during the prevaccination period. The vaccination efficacy found to be 74.68% was lower the efficacy determined from seroconversion studies.


[Molecular analysis of chronic Philadelphia chromosome negative myeloid leukemia: study of 6 cases]. Patients with Philadelphia negative (Ph-) chronic myeloid leukemia (CML) constitute a small proportion of the total number of patients with CML. Molecular analysis of these cases has permitted recognition that some cases present a breakpoint in the bcr region of chromosome 22, that is, the alteration constituting the substrate of the Ph chromosome. To date, the number of patients analyzed to this regard is low. Six patients with Ph negative CML who constituted part of a series of 96 patients diagnosed with CML over a period of 6 years were studied. Analysis of the BCR gene in the DNA of the leuko-concentrate of peripheral blood was carried out with the Southern Blot technique, using the 3' and 5' probes and Transprobe and the restriction enzymes Bgl II, Eco RI, Hind III and Bam HI. The principal clinical-hematological characteristics of the patients were analyzed. Breakpoints were observed in the bcr region of chromosome 22 in 3 of the 6 patients, all of whom presented typical CML clinical-hematological features. Half of the patients with Philadelphia negative (Ph-) chronic myeloid leukemia (CML) have a breakpoint in the bcr region of chromosome 22, a similar molecular pattern to the Ph positive CML and their clinical-hematological profile is indistinguishable from those with CML.


[Drug consumption in diabetes mellitus (I). Estimate of the therapeutic profile and the prevalence in the regions of Tarragona (548,900 inhabitants). Grup per a l'Estudi de la Diabetis a Tarragona]. This study was carried out to estimate the treatment characteristics and prevalence of diabetes mellitus (DM) diagnosed in the counties of Tarragona (548,900 inhabitants) from the consumption of hypoglycemic medication. A stratified aleatory sample was made of the prescription of oral hypoglycemic agents (OHA) and insulin (INS) in 14 centers of primary health care. Calculation of pharmacy dispensing and prescriptions (computer network of the Institut Català de la Salut) was carried out with a relation of the mean doses of the survey and the estimate of the consumer population being made. A contrast was made of the system with the daily doses defined (DDD/1,000 inhabitants/day) of the different OHA and INS preparations. Following aleatorization a representative sample of 550 diabetics, 64 (11.6%) type I and 486 (88.4%) type II was obtained. In total, 61 were treated with diet alone (IC 95%; 8-13%, p less than 0.05); 249 (41-49%) with OHA (51% of type II) and 240 (39-47%) received insulin, all the type I and 176 (36%) type II. In 23 cases (2-5%) multiple therapy with different drugs was confirmed and 72 (10-15%) were treated with the maximal doses of OHA recommended. The rate of OHA/INS was 2.02-2.05. The prevalence of pharmaco-treated DM was 1.9% (prescriptions of public health) and 2.1-2.3% (total consumption). The method for DDD was evaluated as between 1.8% (prescriptions) and 2.0% (total consumption). Globally, during 1990 the prevalence of DM diagnosed in Tarragona was estimated as between 2.1-2.5%. The estimation of the prevalence of diabetes mellitus indicated higher numbers than those obtained in other studies providing a first line indicator for the planning of care for diabetics in this demarcation. The study also identified the real therapeutic tendencies permitting the extraction of lines of action for the education of diabetics and the formation of professionals attending these patients.


Laser stapedotomy: a comparative study of prostheses and seals. During the past 13 years, a number of prostheses of differing design and tissue seals have been used in laser stapedotomy for otosclerosis. This study compares the results of three different configurations of prostheses and tissue seals in a series of 53 patients. In 19, a platinum wire Teflon piston was placed in the laser stapedotomy fenestra and crimped on the long process of the incus; autologous venous blood was infiltrated into the oval window niche as a sealing mechanism. In 8 patients, a stainless steel bucket-handle-type prosthesis was used with a blood tissue seal. In 26 patients, a segment of autogenous vein was clad onto the bucket-handle-type prosthesis and placed into the laser fenestra. Two tissue seals (blood and vein) were also compared. The results were compared with regard to several audiometric parameters. It would appear that the bucket handle/vein configuration improves air-bone gap closure in the low- and mid-frequency speech range and also shows an advantage for air-bone gap closure to 10 dB or less compared to the other configurations in this study. Mean postoperative gaps were significantly less for vein compared to the blood tissue seal. Physiologic and surgical implications are discussed, and the vein-clad technique is illustrated.


Same-day-stay head and neck surgery.

Same-day-stay head and neck surgery. The purpose of this study was to determine if selective head and neck surgical procedures on a same-day basis are justifiable. Two hundred consecutive head and neck same-day procedures were reviewed, including 84 parotidectomies and 116 other procedures previously managed as inpatients. Of the 200 patients, 36 (18%) were admitted, 33 for overnight observation, and 164 (82%) were discharged the same day. There were no complications reported in the discharged patients and a later questionnaire showed that 97% of the patients were satisfied. The advantages of selective same-day procedures outweigh the disadvantages for otolaryngologist and patient. The study shows that same-day-stay head and neck surgery for selective procedures is safe, reasonable, and cost-effective, but the combined efforts of the otolaryngologists, nurses, and administrators are required. Because of rising healthcare costs, experts are predicting a significant increase in the next few years of outpatient surgery, including surgery of the head and neck.


Classification of laryngotracheal stenosis. Seventy-two cases of laryngotracheal stenosis treated from 1981 through 1991 were reviewed to develop a system of classification which would be useful in predicting the outcome of treatment. Decannulation and absence of dyspnea after exertion were the criteria of successful management. The probability of decannulation over time was computed using the Kaplan-Meier technique. Cox multiple regression analysis was used to determine the effects of independent variables (age, sex, etiology, site of stenosis, length of stenosis, diameter of stenosis, and surgical technique) on treatment success. The only factors with a significant effect on the outcome were site of stenosis and diameter of stenosis. A classification into four clinical stages of stenosis based on site of lesion was shown to effectively predict the likelihood of successful decannulation.


The management of subglottic stenosis in patients with Wegener's granulomatosis. Wegener's granulomatosis (WG) is a multisystem inflammatory disease characterized by vasculitis, granuloma formation, and necrosis. Among 158 patients treated at the National Institutes of Health during the past 24 years, 145 (92%) had an otolaryngologic manifestation of their disease and 25 (16%) had subglottic stenosis (SGS). SGS varied from asymptomatic to life-threatening. Sixteen (80%) of 20 patients with fixed SGS required surgical intervention, including manual dilations, carbon-dioxide laser resections, and laryngotracheoplasty (LTP). LTP was performed with and without microvascular reconstruction. Thirteen of the patients required tracheostomy and all 13 were ultimately decannulated. Five patients who repeatedly failed dilations and/or endoscopic laser surgery underwent LTP. Since 1987, two patients have undergone LTP with microvascular free flaps. Both patients were subsequently decannulated. The authors' experience demonstrates that management of SGS in WG is complex, requiring individualized frequent multimodality interventions to achieve satisfactory results. Microvascular laryngotracheal reconstruction should be considered in the surgical armamentarium for patients with persistent stenoses.


Thermal effects on horseradish peroxidase uptake in laser nerve transections. The authors previously reported that rat tibial nerves transected with CO2 or KTP/532 laser transmit less horseradish peroxidase (HRP) than those transected with a scalpel. This may be due to laser-specific effects or to thermal phenomena that are laser-independent. This study investigated potential thermal effects on the transmission of HRP through the tibial branch of the sciatic nerve in rats. Bilateral nerve transections were performed on 18 animals using a scalpel (control) or an electrocautery device, which simulated the thermal effects produced by lasers. HRP retrograde transport and deposition in the rat spinal cord were analyzed. Thirteen of 15 animals showed a higher number of HRP-labelled neurons on the scalpel side compared to the electrocautery side; a paired student's t test showed a significant difference (P = .028) in the numbers of HRP-stained cell bodies between the control group (x = 687.13 +/- 119.3) and the electrocautery group (x = 388.1 +/- 111.2). In conclusion, reduced HRP uptake in tibial nerves transected with lasers may be in part due to thermal effects produced by the lasers.


Cholesteatoma in the pediatric population: prognostic indicators for surgical decision making. A review of surgical therapy for pediatric cholesteatoma at the Arkansas Children's Hospital was performed. Fifty-three children treated surgically for cholesteatoma were studied over a 10-year period. Primary acquired, or attic retraction cholesteatomas, were generally treated with a canal up tympanomastoidectomy; there were very few complications or secondary procedures in this group. Middle ear or secondary acquired cholesteatomas were initially treated by both canal up and canal down procedures; however, a large percentage of these patients eventually required an open cavity procedure. The presence of cholesteatoma in the sinus tympani strongly predicted failure to control disease with a canal up procedure (P < .05); conversely, the absence of matrix in the sinus tympani was predictive for success when a canal up procedure was used for attic cholesteatoma (P < .05). Finally, it was determined that follow-up was not adequate in our patient population. With this in mind, guidelines for the management of pediatric cholesteatoma will be presented.


Surgical management of the thyroid nodule: patient selection based on the results of fine-needle aspiration cytology. To determine whether the routine use of fine-needle aspiration (FNA) cytology reduces the rate of unnecessary surgery, the surgical pathology of 54 thyroidectomy patients who had preoperative FNA was compared to the results obtained with 24 thyroidectomy patients who did not have preoperative FNA. Twenty-nine (85.3%) of the 34 patients who had a positive FNA were confirmed by histology to have a thyroid neoplasm; in 24 patients, the neoplasm was malignant. Two of the 17 patients who had a negative FNA but underwent thyroidectomy based on other factors were found to have thyroid cancer. Only 8 (33.3%) of the 24 surgical specimens of patients who did not have an FNA were found to be malignant. FNA had a sensitivity of 93.5% and a specificity of 75.0%. The results indicate that the routine use of FNA for patients with thyroid nodules reduces the incidence of unnecessary surgery. Furthermore, FNA alone is sufficient to identify most patients at risk and is, therefore, cost-effective. However, the presence of other findings suspicious of malignancy should preclude clinical decision making based on FNA alone.


Hearing preservation following surgical removal of meningiomas affecting the temporal bone. It is a common clinical impression that preservation of hearing is more often achieved when removing a meningioma than a similarly sized acoustic tumor. However, relatively few reports have focused on postoperative hearing results after meningioma removal, and detailed audiometric data are not commonly provided, particularly in the neurosurgical literature. During the past 16 years, 56 meningiomas affecting the temporal bone have been surgically removed at the House Ear Clinic. Hearing preservation was attempted in 16 (29%) of the 56 cases, and these were the focus of this study. The primary presenting symptom was otologic in 67% of these cases, including hearing loss as the primary symptom in 27%. Measurable postoperative hearing was present in 11 (92%) of 12 patients with postoperative audiograms available, and 8 (67%) of 12 patients had good hearing postoperatively. Hearing was preserved near the preoperative level (within 10 dB speech reception threshold and 15% speech discrimination) in 75% of cases.


Petrous apex cholesteatoma: diagnostic and treatment dilemmas. The diagnosis and treatment of petrous apex cholesteatoma is a difficult surgical challenge. This study is a review of 14 cases of cholesteatoma involving the petrous apex. These cholesteatomas originated as a congenital primary lesion or secondary to an acquired lesion. The cases were evaluated according to the clinical features, the intraoperative findings, the radiological findings, and the surgical approaches. In this series, 83% of the patients presented with hearing loss and 50% presented with facial nerve weakness or paralysis (House grade II to VI). Intraoperative and radiological features revealed frequent direct labyrinthine and supralabyrinthine cell spread. The transpetrous surgical approach was used in all cases. The main factors affecting the surgical approach to be adopted are the inaccessible nature of the petrous apex, the extent of disease, the degree of facial nerve function, and the need for the prevention of cerebrospinal fluid leaks and the recurrence of the lesion.


Advanced carcinoma of the tongue: total glossectomy without total laryngectomy. Review of 80 cases. Opinions are divided over the validity of total glossectomy without associated total laryngectomy for advanced carcinoma of the tongue. This retrospective study evaluates the oncologic and functional results obtained in 80 patients who underwent total glossectomy as a primary procedure or as salvage surgery. Satisfactory swallowing ability was obtained in 41 patients, and speech was understandable in 49 patients. The survival rate at 1 year was 65%, with early recurrence of the disease, which was especially frequent in patients with prior radiotherapy, being the major cause of death. The study confirms the poor prognosis of cases with mandibular involvement, and the fact that partial laryngectomy, when required, impairs functional results. In the light of the authors' experience, total glossectomy without total laryngectomy should only be undertaken in motivated and well-supported patients able to accomplish the difficult rehabilitation process.


Amyloid of the facial nerve.

Amyloid of the facial nerve. Although facial nerve paralysis has been reported in association with amyloidosis, histologic confirmation of facial nerve involvement with amyloid has not been previously demonstrated. A case of localized primary amyloidosis of the facial nerve is presented, and a new magnetic resonance technique for imaging the facial nerve is described.


Prognostic factors, outcomes and staging in ethmoid sinus surgery. Although the literature is replete with papers discussing the results of surgery for chronic inflammatory sinus disease, critical comparison of results is difficult due to limited knowledge of the prognostic factors and the variable criteria reported for success. Detailed prospective and retrospective data collection was therefore undertaken to evaluate the results of surgical intervention in 120 patients who underwent endoscopic sinus surgery. Results were evaluated both by symptom questionnaire and by endoscopic follow-up examination. Over 240 data fields were collected on each patient, including information regarding presenting symptoms, endoscopic and computed tomography (CT) findings and surgical procedures performed. In order to reduce potential bias, the results of the follow-up questionnaires were compared to questionnaires from other patients unable to return for follow-up endoscopy. Mean follow-up time was 18 months. Potential prognostic variables were evaluated statistically. A strong correlation was identified between the extent of disease and the surgical outcome. Other identified potential factors appeared to have little or no significance. Therefore, a staging system for inflammatory sinus disease based on the extent of disease is suggested.


Initial results of endothelial cell seeding following argon laser carotid endarterectomy. This study evaluates the initial results of endothelial cell (EC) seeding following argon laser carotid endarterectomy. Venous endothelial cells were harvested from 12 dogs and cultured. A laser endarterectomy was performed on both carotids of each dog. One side was seeded with endothelial cells. Six dogs had both carotids harvested 1 hour after restoring blood flow. The others were harvested in 24 hours. The percentage of lumen covered with EC was evaluated by scanning electron microscopy. At 1 hour, the seeded arteries demonstrated 35 +/- 3 percent EC coverage, whereas the unseeded arteries had no EC coverage (P = 0.0002). At 24 hours, the seeded arteries had 58 +/- 15 percent EC coverage, whereas the unseeded arteries had no coverage (P = 0.01). Significant gross thrombus developed only in unseeded arteries (P = 0.047), two of which were occluded at 24 hours. EC seeding is beneficial following argon laser carotid endarterectomy resulting in improved patency and less surface thrombogenicity.


Effect of force on ablation depth for a XeCl excimer laser beam delivered by an optical fiber in contact with arterial tissue under saline. The effect of force applied to a 430 micron single fiber, delivering 60 pulses of 308 nm XeCl laser radiation at 20 Hz, on the ablation depth in porcine aortic tissue under saline has been investigated. Energy densities of 8, 15, 25, 28, 31, 37, and 45 mJ/mm2 were used. Force was applied by adding weights from 0 to 10 grams to the fiber. The fiber penetration was monitored by means of a position transducer. At 0 grams, the ablation depth increased linearly with incident energy density, but the fiber did not penetrate the tissue; with any weight added, the fiber penetrated the tissue at energy densities above 15 mJ/mm2. The fiber did not penetrate during the first several pulses, possibly due to gas trapped under the fiber. After these first pulses, a smooth linear advancement of the fiber began, which lasted until the pulse train stopped. The ablation depth increased with increasing energy densities and weights. This effect was largest above 25 mJ/mm2 where the ablation efficiencies (unit mm3/J), with weights added to the fiber, were substantially larger than values found in 308 nm ablation experiments described in the literature, which were conducted with either a focused laser beam or a fiber without additional force. The results imply that in 308 nm excimer laser angioplasty, force must be applied to the beam delivery catheter for efficient recanalization, and that experiments performed with a focused beam or without actual penetration of the fiber do not represent the situation encountered in excimer laser angioplasty.


XeCl laser ablation of atherosclerotic aorta: optical properties and energy pathways. The energetics of 308-nm excimer laser irradiation of human aorta were studied. The heat generation that occurred during laser irradiation of atherosclerotic aorta equaled the absorbed laser energy minus the fraction of energy for escaping fluorescence (0.8-1.6%) and photochemical decomposition (2%). The absorbed laser energy is equal to the total delivered light energy minus the energy lost as specular reflectance (2.4%, air/tissue) and diffuse reflectance (11.5-15.5%). Overall, about 79-83.5% of the delivered light energy was converted to heat. We conclude that the mechanism of XeCl laser ablation of soft tissue involves thermal overheating of the irradiated volume with subsequent explosive vaporization. The optical properties of normal wall of human aorta and fibrous plaque, both native and denatured were determined. The light scattering was significant and sufficient to cause a subsurface fluence (J/cm2) in native aorta that equaled 1.8 times the broad-beam radiant exposure, phi o (2.7 phi o for denatured aorta). An optical fiber must have a diameter of at least 800 microns to achieve a maximum light penetration (approximately 200 microns for phi o/e) in the aorta along the central axis of the beam.


Cornea epithelial damage thresholds in rabbits exposed to Tm:YAG laser radiation at 2.02 microns. We have determined exposure conditions for minimal damage to the corneal epithelium in rabbit using a continuous wave Tm: YAG laser operating in the TEM00 mode at incident powers between 80 and 450 mW. The 1/e beam diameter was 0.94 mm and exposure durations for threshold damage ranged from 4.3 to 0.08 sec. Calculated temperature increases on the beam axis 10 microns beneath the surface at the measured thresholds were essentially constant and averaged 44 degrees C. This is basically the same temperature increase found for threshold CO2 laser damage and suggests that the critical temperature damage model, which correlates CO2 laser damage, can predict damage thresholds for mid-infrared laser radiation. We also showed that reliable thresholds can be determined in freshly enucleated eyes, thus opening up the possibility of using available laser sources in laboratories not equipped and approved for animal experiments to determine damage thresholds.


Immediate retinal adhesion by CO2 laser irradiation using a fiberoptic intraocular probe. Using an experimental fiberoptically guided CO2 laser system, we produced lesions on fresh bovine retinas. These lesions were shown to achieve immediate measurable chorioretinal adhesion. This model provides preliminary data on the use of a fiberoptic CO2 laser probe to produce chorioretinal lesions and possible future use in intraocular surgery for retinal detachment. The advantages of using CO2 laser energy are minimal damage surrounding desired lesion and its versatility as a coagulator and cutter. With modifications, CO2 endolaser may have a role in intraocular surgery.


Laser-induced experimental vascular occlusion using liposome-encapsulated ADP. The therapeutic occlusion of retinal vessels is often helpful in treating various pathological conditions. We compared the combined effects of argon laser photocoagulation and adenosine diphosphate (ADP) released from temperature-sensitive liposomes with argon laser photocoagulation alone on occlusion of retinal vessels in pigmented rats. In Group A, 8 eyes were treated with liposome-encapsulated ADP and laser photocoagulation. In Group B, 8 eyes were treated with laser photocoagulation alone. The laser parameters (power, spot size, exposure time) were maintained at the same levels for both groups. The laser was focused on the retinal vessels at the optic nerve head. The treated retinal vessels were observed at time zero, day 1, day 4, and weekly for a period of 3 months. At time zero, 6 of 8 eyes were totally occluded in Group A, with best results obtained at 80 mW. Only 1 of 8 eyes in Group B achieved total occlusion. After 3 months, 4 of 8 eyes in Group A remained totally occluded; no eyes in Group B were occluded. Complete and permanent occlusion of retinal vessels can be achieved by using ADP and laser photocoagulation of lower power density than traditional laser photocoagulation alone.


Effects of rapid pulsed CO2 laser beam on cortical bone in vivo. Twenty rabbit femurs were used to study the effect of CO2 laser on cortical bone. Sixteen femurs were treated with 20 watts, 3 mm defocused beam, 2 KHZ spike pulse mode CO2 laser for 10 seconds through a circular window in the metaphysis. In four control femurs, the inner cortex was exposed without laser treatment. The animals were killed at 4 and 6 weeks and the specimens studied histologically. All laser-treated specimens showed thermal changes. Three histological zones were observed. A superficial zone of inner cortex close to the beam consisted mainly of carbonization or carbon ash during resorption. An intermediate zone consisted of bone necrosis and healing with associated areas of new bone formation. The deep zone of outer cortex had normal bone with no cellular damage. No such changes were observed in the control specimens. The CO2 laser can be used to generate a controlled zone of tissue ablation, which may make it a potentially useful tool for tumor margin cauterization.


Percutaneous laser discectomy with the Ho:YAG laser. A prototype Ho:YAG (2.15 microns) laser operating at 2-J/pulse, 3 Hz through a 600-microns fiber was employed to perform laser discectomies at the L3-4 disc through an 18G needle in five juvenile pigs. No temperature elevations were recorded in the posterior longitudinal ligament at the disc level and all animals recovered fully with no adverse sequelae, even immediately upon awakening from anesthesia. Pathologic examination demonstrated a wide swath of coagulation necrosis confined to the disc space. The Ho:YAG laser, owing to its close approximation to the intense 2.0 microns absorption band of water, appears to be a viable candidate for clinical trials of laser discectomy.


Er:YAG laser ablation of enamel and dentin of human teeth: determination of ablation rates at various fluences and pulse repetition rates. A pulsed Er:YAG laser (2.94 microns) was used to determine ablation depths per pulse of laser energy at 2 Hz and 5 Hz in human teeth cross sections of enamel and dentin. Ablation depths per pulse at 2 Hz in enamel of intact human teeth were measured and compared to ablation depths per pulse determined in enamel cross sections at 2 Hz. Close correlation was observed for ablation depths per pulse of laser energy between teeth cross sections and intact teeth for enamel. Photographs of lased holes at 2 Hz and 5 Hz indicated minimal thermal effects in enamel at fluences below 80 J/cm2. Minimal thermal effects in dentin were noted below 74 J/cm2. Scanning Electron Microscopy (SEM) pictures of lased dentin showed an irregular serrated surface. Results of this study suggest that the Er:YAG laser can effectively ablate enamel and dentin with minimal thermal effects at 2 Hz and 5 Hz.


Centering balloon to improve esophageal photodynamic therapy. A cylindrical balloon was developed to improve delivery of circumferential light for photodynamic therapy (PDT) of esophageal carcinoma. The balloon consisted of a 36-mm-long clear cylindrical membrane and a central tube to hold a cylindrical diffuser in the center of the lumen. Three isotropic probes were placed on the outside of the balloon to allow measurement of delivered light dose to the esophageal mucosa. The balloon was tested in the normal esophagus of 8 dogs that were injected with 4.0 mg/kg of PHOTOFRINR. Endoscopy was performed 48 hours following the injection, and under endoscopic observation the balloon assembly was passed, fixed in place, and inflated. A 1-cm cylindrical diffuser was passed into the central tube and 150, 300, and 600 Joules/cm of 630 nm laser light was delivered at 25 cm, 15 cm, and 5 cm proximal to the gastroesophageal junction. One control dog was illuminated using the cylindrical diffuser alone at doses of 300 and 600 Joules/cm of diffuser. Complete circumferential tissue response was obtained when the balloon was used. Relatively uniform light intensities were measured around the lumen. In contrast, noncircumferential and unpredictable PDT responses were generated when the cylindrical diffuser was used without the balloon.


CO2 laser urethroplasty in the rabbit: a preclinical model. Our previous work has shown that the CO2 laser can be successfully used in urethral reconstruction in a rat model. This new experiment investigates the use of the CO2 laser to perform a patch graft urethroplasty in the rabbit, as a preclinical model to its use in the repair of hypospadias in humans. Using sterile technique, a patch graft of preputial skin was welded in the repair of a standardized urethral defect in 10 rabbits. In another cohort, the same urethral defect was repaired using standard microsuture technique. In a control group the patch graft was placed with microsuture in a nonwatertight fashion. All animals were followed for 3 weeks. Histologic and radiologic analyses were done in a blinded fashion. Our study showed that CO2 laser repair, when compared to microsuture in urethral reconstruction, required 40% less operative time and produced better graft healing and less intraluminal scarring.


Interstitial Nd:YAG laser ablation in normal rabbit liver: trial to maximize the size of laser-induced lesions. In order to apply interstitial laser ablation to relatively small liver tumors in humans, it will be necessary to optimize the irradiation schedule. Nd:YAG laser was applied to normal rabbit liver in vivo at various power and energy outputs, including a protocol in which irradiation was repeated twice, with and without fiber tip advancement during the intermission. Ex vivo and in vivo tissue were also irradiated to determine the effect of perfusion on the lesion size. We obtained the same monotonic relationship between laser settings and lesion size in rabbit liver as we previously reported in rat liver. MR-guided fiber advancement between heating periods increased the transverse diameter of the lesion, and MR monitoring demonstrated this process. Our results suggest that repeated irradiation with brief intermissions, when combined with fiber advancement, may increase the lesion size.


Interstitial laser photocoagulation: Nd:YAG 1064 nm optical fiber source compared to point heat source. Interstitial laser photocoagulation (ILP) was performed in vitro in lean bovine and chicken muscle by delivering 1.6 W of continuous-wave Nd:YAG laser energy (1064 nm) from a 400-microns core optical fiber for 300s. The resulting thermal coagulation lesion was consistently larger when the delivered energy was deposited into a small steel sphere than when it was delivered freely into the tissue. Mathematical modelling confirms this result. This preliminary study suggests that a point heat source produces a larger volume of thermal coagulation than a point optical source (1064 nm) delivering the same power.


Locomotory characteristics of fibroblasts within a three-dimensional collagen lattice: modulation by a helium/neon soft laser. It has been postulated that low energy (soft) lasers can enhance wound healing. Considering the importance of cell locomotion in the wound healing process, we have studied the effects of a helium/neon laser upon the locomotory behaviour of a population of fibroblasts migrating within a three-dimensional hydrated collagen lattice. Statistical methods were used to quantify cell three-dimensional trajectories obtained using a computer-assisted tracking system. A two-minute exposure of embryonic fibroblasts to soft laser light decreased the speed and increased the frequency and duration of stops compared to controls. The locomotory phenotype induced in embryonic fibroblasts by the laser light resembled that of the developmentally older c20 fibroblasts, which are known to express a more mature locomotory phenotype. The relevance of these results to wound healing is discussed.


Laser reflections from surgical instruments. The potential hazards to the eye and skin from accidental exposures caused by reflected laser beams from surgical instruments has long been of concern to operating room staff members. Reflectance values for argon neodymium:YAG and CO2 laser wave-lengths were measured from 29 reference surfaces used on surgical instruments. From these measurements, nominal hazard zones could be determined for typical reflection hazards.


Local anesthetic-induced toxicity may be modified by low doses of flumazenil. The purpose of this study was to investigate the influence of flumazenil on local anesthetic-induced acute toxicity. For each of the three tested anesthetics (etidocaine, mepivacaine and lidocaine) 6 groups of mice were treated by a single dose of flumazenil (0.125, 0.25, 0.5, 1 and 2 mg/kg), or an equal volume of saline, 15 minutes before the injection of the anesthetic (etidocaine: 50 mg/kg, mepivacaine: 110 mg/kg and lidocaine: 115 mg/kg). The convulsant activity, the time of latency to convulse and the mortality rate were assessed in each group. The local anesthetic-induced mortality was not significantly modified by flumazenil. The convulsant activity of lidocaine and mepivacaine was significantly increased by flumazenil but not for etidocaine. Also, increasing doses of flumazenil decreased the time of latency to obtain lidocaine-induced convulsions. This effect was not obtained with etidocaine or mepivacaine.


The effect of lowered extracellular Na+ concentration on ultraviolet light-induced relaxation of vasoconstricted rabbit isolated thoracic aorta. The effect of lowering extracellular ion concentration on ultraviolet (UV) light-induced photorelaxation of norepinephrine(NE)-constricted rabbit isolated thoracic aorta was investigated. The magnitude of the photorelaxation response (similar to acetylcholine-induced, but not nitroprusside-induced, relaxation) progressively declined, in the absence of an effect on NE-induced vasoconstriction, as the total extracellular ion concentration was progressively reduced. This diminution in the photorelaxation response was duplicated by isosmotic lowering of the extracellular concentration of Na+, but not other ions, from 145 to 25 mM and was not restored by the replenishment of the Na+ deficiency by equimolar amounts of mannitol or Li+. In contrast, choline fully substituted for Na+. These findings suggest a fundamental difference in the ion dependency (and, hence, the mechanisms) of UV-induced photorelaxation and the vasorelaxations induced by acetylcholine or sodium nitroprusside.


The effect of FK664, a new cardiovascular drug, on systemic capacitance vessels in anesthetized dogs. To characterize the cardiovascular effect of FK664, a compound developed for the treatment of heart failure, the mean circulatory pressure (MCP), cardiac output and other parameters were measured in open-chest anesthetized dogs. Milrinone, a cardiotonic agent, and nifedipine, a calcium channel blocker were used as reference substances. Nifedipine (10 micrograms/kg), FK664 (0.1 mg/kg) or milrinone (0.1 mg/kg) given intravenously reduced the total peripheral resistance in a similar extent (35-40%). Whereas nifedipine had no effect on MCP, FK664 produced a significant decrease in MCP. Milrinone caused a minimal decrease in MCP, but not significantly. These results indicate that FK664 dilates the systemic capacitance vessels. This action to reduce the pre-load would be beneficial in the treatment of heart failure.


Amylin.

Amylin. Amylin is a 37 amino-acid peptide which is secreted from the pancreatic islets of Langerhans. It has major sequence homology with calcitonin gene related peptide. Amylin can precipitate out in these cells to form amyloid. Amylin is secreted by similar stimuli to those that secrete insulin. Amylin has a number of effects that may counteract the effect of secreted insulin, i.e., decreased second phase insulin secretion, increased hepatic glucose output, and inhibition of insulin effects on skeletal muscle. It must, however, be recognized that in many cases the doses necessary to produce these effects appear to be supraphysiological. The putative role of amylin in the hyperglycemia of aging and Type II diabetes mellitus therefore remains controversial. Amylin has a number of other effects including inhibition of osteoclastic activity, vasodilatation, anorectic effects and enhanced memory retention. This review postulates a role for amylin in the pathogenesis of a number of age-related changes.


Long-term effects of aluminium on the fetal mouse brain. Potentially noxious substances may act as fetal teratogens at levels far lower than those required to produce detectable effects in adults, and behavioural teratogenicity may occur at levels lower than those which produce morphological teratogenesis. Aluminium (Al) is a potential neurotoxin in adults. Since pregnant women may be exposed to untoward levels of Al compounds under certain conditions, we have examined the long-term effects of treating the pregnant mouse with intraperitoneal or oral aluminium sulphate on brain biochemistry and behaviour of the offspring. The cholinergic system, as evaluated by the activity of choline acetyltransferase (ChAT), was affected differentially in different regions of the brain, and still showed significant effects in the adult. Differences between the intraperitoneal and oral series in the magnitude of effect seen in the regions of the brain probably reflect differences in the effective level of exposure. Growth rate and psychomotor maturation in the pre-weaning mouse were affected in the intraperitoneal series only, showing a marked post-natal maternal effect.


Combination therapy with an antioxidant and a corticosteroid prevents autoimmune diabetes in NOD mice. Oxygen free radicals have been implicated as mediators of pancreatic islet beta cell damage in autoimmune, insulin-dependent diabetes mellitus (IDDM). In this study, we show that the antioxidant, probucol, produced only a small decrease in diabetes incidence in nonobese diabetic (NOD) mice, an animal model for human IDDM. However, combination of probucol with the antiinflammatory corticosteroid, deflazacort, produced an early synergistic effect, delaying diabetes onset by 3 weeks, and a later additive effect, decreasing diabetes incidence from 68% (17 of 25 mice) to 23% (6 of 26 mice, p < 0.005). Protection against diabetes by the combination of probucol and deflazacort was associated with a significant decrease in pancreatic islet infiltration by macrophages/lymphocytes (insulitis) and prevention of islet beta cell loss.


Increase of plasma IL-6 concentration with age in healthy subjects. The present study demonstrated that plasma IL-6 concentration was higher in older subjects than in younger ones and significantly in the male group (P = 0.02); Spearman rank correlation showed that plasma IL-6 concentration was positively correlated with age (r = 0.28, N = 55, P < 0.05); there was a highly significant correlation between the concentrations in plasma IL-6 and IL-1 alpha (r = 0.51, N = 52, P < 0.001). These findings suggest the possibility that age-related changes of plasma IL-6 and IL-1 alpha may provide a pathological basis for the susceptibility to such illness as commonly occurs in elderly people, especially Alzheimer's disease as the two interleukins can induce the production of alpha 1-antichymotrypsin and beta-amyloid protein precursor.


PMA-sensitive protein kinase C is not necessary in TRH-stimulated prolactin release from female rat primary pituitary cells. In GH3 cells and other clonal rat pituitary tumor cells, TRH has been shown to mediate its effects on prolactin release via a rise of cytosolic Ca2+ and activation of protein kinase C. In this study, we examined the role of protein kinase C in TRH-stimulated prolactin release from female rat primary pituitary cell culture. Both TRH and PMA stimulated prolactin release in a dose-dependent manner. When present together at maximal concentrations, TRH and PMA produced an effect which was slightly less than additive. Pretreatment of rat pituitary cells with 10(-6) M PMA for 24 hrs completely down-regulated protein kinase C, since such PMA-pretreated cells did not release prolactin in response to a second dose of PMA. Interestingly, protein kinase C down-regulation had no effect on TRH-induced prolactin release from rat pituitary cells. In contrast, PMA-pretreated GH3 cells did not respond to a subsequent stimulation by either PMA or TRH. Pretreatment of rat pituitary cells with TRH (10(-7) M, 24 hrs) inhibited the subsequent response to TRH, but not PMA. Forskolin, an adenylate cyclase activator, stimulated prolactin release by itself and in a synergistic manner when incubated together with TRH or PMA. The synergistic effects of forskolin on prolactin release was greater in the presence of PMA than TRH. Down-regulation of protein kinase C by PMA pretreatment abolished the synergistic effect produced by PMA and forskolin but had no effect on those generated by TRH and forskolin. sn-1,2-Dioctanylglycerol (DOG) pretreatment attenuated the subsequent response to DOG and PMA but not TRH. The effect of TRH, but not PMA, on prolactin release required the presence of extracellular Ca2+. In conclusion, the mechanism by which TRH causes prolactin release from rat primary pituitary cells is different from that of GH3 cells; the former is a protein kinase C-independent process whereas the latter is at least partially dependent upon the activation of protein kinase C.


5c,11c,14c-eicosatrienoic acid and 5c,11c,14c,17c-eicosatetraenoic acid of Biota orientalis seed oil affect lipid metabolism in the rat. The effects of 5c,11c,14c-eicosatrienoic acid (20:3BSO) and 5c,11c,14c,17c-eicosatetraenoic acid (20:4BSO), polyunsaturated fatty acids (PUFA) contained in Biota orientalis seed oil (BSO), on lipid metabolism in rats were compared to the effects of fats rich in linoleic acid (LA) or alpha-linolenic acid (ALA) under similar conditions. The potential effect of ethyl 20:4BSO as an essential fatty acid also was examined in comparison with the ethyl esters of LA, ALA and gamma-linolenic acid (GLA). BSO- and ALA-rich fat decreased the concentration of plasma total cholesterol, high density lipoprotein cholesterol, triglyceride and phospholipid as compared to LA-rich fat. BSO was more effective in reducing plasma cholesterol concentrations than was the ALA-rich fat. Dietary BSO markedly decreased the hepatic triglyceride concentration as compared to the LA-rich or ALA-rich fats. Aortic production of prostaglandin I2 tended to decrease in rats fed BSO or ALA-rich fat compared to those fed the LA-rich fat. Adenosine diphosphate-induced platelet aggregation was similar in the three groups. The proportion of arachidonic acid (AA) in liver phosphatidylcholine (PC) of rats fed BSO was lowest compared to that of rats fed ALA-rich or LA-rich fats. Administration of 20:4BSO, ALA or GLA to essential fatty acid-deficient rats decreased the ratio of 20:3n-9 to AA in liver PC to the same extent; administration of LA was more effective. The results indicate that the effects of specific PUFA contained in BSO on lipid metabolism are different from those of LA and ALA. It is also suggested that 20:4BSO may exhibit some essential fatty acid effects.


Inhibitory effect of curcumin on fatty acid desaturation in Mortierella alpina 1S-4 and rat liver microsomes. An extract of rhizomes of Curcuma longta L. (turmeric) inhibited the desaturation of dihomo-gamma-linolenic acid (DGLA) in the arachidonic acid (AA) producing fungus Mortierella alpina 1S-4. The factor responsible for this phenomenon was isolated and identified as curcumin (diferuloyl methane). Mycelial DGLA levels increased about two-fold (22.3 mg/g dry weight) with a concomitant decrease in AA levels when the fungus was cultivated with curcumin. The 50% inhibitory concentration against delta 5 desaturase was 27.2 microM. Curcumin also inhibited rat liver microsomal delta 5 and delta 6 desaturases.


Nonesterified fatty acids in normal and diabetic rat sciatic nerve. Alloxan-induced diabetes in rats results in elevated levels of nonesterified fatty acids (NEFA) in whole sciatic nerve and its endoneurium. Increases in NEFA levels are more pronounced in whole diabetic nerve (40% over control) than in its endoneurial portion (20-30%). Alterations in the composition of phospholipid fatty acids are observed as well, including an increase in linoleate (18:2n-6) in endoneurial phosphatidylethanolamine and a decrease in arachidonate (20:4n-6) in both phosphatidylethanolamine and phosphatidylinositol of diabetic nerve.


Dietary fat and fatty acids modulate cholesterol cholelithiasis in the hamster. We tested two hypotheses, i) whether the type and the amount of fat in the diet will affect the formation of cholesterol gallstones in the hamsters, and ii) whether palmitic acid, a major fatty acid component of butterfat, can act as a potentiator of cholesterol cholelithiasis in the hamster. Young, male golden Syrian hamsters (Sasco) were fed a semipurified diet containing casein, corn starch, cellulose and cholesterol (0.3%) to which various types and amounts of fat (butterfat, olive oil, menhaden oil, corn oil) were added. All diets contained 2% corn oil to supply essential fatty acids to the growing hamsters. No deaths or illness occurred during the experiment. Animals fed the semipurified diet plus 4% butterfat (group 1) had a gallstone incidence of 63%. Replacement of butterfat with either olive oil, corn oil or menhaden oil prevented the formation of cholesterol gallstones entirely (groups 2-4). When total butterfat was increased from 4% to 8% (group 8), the incidence of cholesterol gallstones increased to 80%. Substitution of 4% olive oil (group 5), corn oil (group 6), or menhaden oil (group 7) for the additional 4% butterfat significantly reduced gallstones to 35%, 45% and 30%, respectively. The replacement of 4% butterfat with 1.2% palmitic acid gave the highest incidence of cholesterol gallstones (95%). These results suggest that butterfat (and one of its components, palmitic acid) intensifies gallstone formation in this model whereas mono- and polyunsaturated fats act as inhibitors of cholesterol cholelithiasis. A fatty acid, possibly palmitic acid, appears to act as lithogen in our model.


Changes in blood lipids and fibrinogen with a note on safety in a long term study on the effects of n-3 fatty acids in subjects receiving fish oil supplements and followed for seven years. The present study was designed to assess the effectiveness of the n-3 fatty acids in modifying serum total, low density lipoprotein and high density lipoprotein (HDL) cholesterol, as well as serum triglycerides, over a seven-year period. Changes in plasma fibrinogen were recorded and long term safety assessed. A total of 365 subjects with ischemic heart disease (IHD), hyperlipidemia or a strong family history of IHD had their diet supplemented with MaxEPA (Seven Seas Ltd., Hull, England) fish oil containing 18-19% eicosapentaenoic acid. Venous blood samples were taken at regular intervals for lipid and fibrinogen assays and routine clinical chemistry and hematological profiling. Current medication was recorded and no further dietary modification was attempted. Triglyceride and fibrinogen were significantly reduced, whereas a significant reduction in total cholesterol occurred only in the subjects with a pre-oil level greater than 6.5 mmol/L. HDL cholesterol significantly increased over the study period. Clinical chemistry and hematological profiles were not adversely affected, and platelet count did not change significantly. The type of lipid changes observed were those usually considered antiatherogenic. Reducing fibrinogen may result in beneficial changes in the pathological processes leading to thrombotic occlusion. The consumption of MaxEPA by our patients over a seven-year period did not indicate any adverse effects.