A comparative analysis of parvalbumin expression in pinfish (Lagodon rhomboides) and toadfish (Opsanus sp.).

This study examines the role of a myoplasmic protein, parvalbumin, in enhancing muscle relaxation by fishes. Parvalbumin is thought to bind free Ca(2+) during muscle contraction, thereby reducing intracellular [Ca(2+)] in muscle and speeding muscle relaxation by reducing Ca(2+) availability to the troponin complex. We hypothesized that parvalbumin expression is ubiquitously expressed in fish muscle and that its expression levels and role in muscle relaxation would depend on the activity level and the thermal environment of a given fish species. Muscle contractile properties and patterns of parvalbumin expression were examined in pinfish (Lagodon rhomboides) and two species of toadfish (gulf toadfish, Opsanus beta, and oyster toadfish, Opsanus tau). Unlike another sparid (sheepshead), the active swimming pinfish does not express parvalbumin in its slow-twitch red muscle. However, both sheepshead and pinfish have relatively high levels of parvalbumin in their myotomal white muscle. Gulf toadfish from the Gulf of Mexico expressed higher levels of parvalbumin and had faster muscle relaxation rates than oyster toadfish from more northern latitudes. The faster muscle of gulf toadfish also expressed relatively more of one parvalbumin isoform, suggesting differences in the binding properties of the two isoforms observed in toadfish swimming muscle. Parvalbumin expression and its role in muscle relaxation appear to vary widely in fishes. There are many control points involved in the calcium transient of contracting muscle, leading to a variety of species-specific solutions to the modulation of muscle relaxation.

Morphine preferentially activates the periaqueductal gray-rostral ventromedial medullary pathway in the male rat: a potential mechanism for sex differences in antinociception.

The midbrain periaqueductal gray (PAG), and its descending projections to the rostral ventromedial medulla (RVM), provide an essential neural circuit for opioid-produced antinociception. Recent anatomical studies have reported that the projections from the PAG to the RVM are sexually dimorphic and that systemic administration of morphine significantly suppresses pain-induced activation of the PAG in male but not female rats. Given that morphine antinociception is produced in part by disinhibition of PAG output neurons, it is hypothesized that a differential activation of PAG output neurons mediates the sexually dimorphic actions of morphine. The present study examined systemic morphine-induced activation of PAG-RVM neurons in the absence of pain. The retrograde tracer Fluorogold (FG) was injected into the RVM to label PAG-RVM output neurons. Activation of PAG neurons was determined by quantifying the number of Fos-positive neurons 1 h following systemic morphine administration (4.5 mg/kg). Morphine produced comparable activation of the PAG in both male and female rats, with no significant differences in either the quantitative or qualitative distribution of Fos. While microinjection of FG into the RVM labeled significantly more PAG output neurons in female rats than male rats, very few of these neurons (20%) were activated by systemic morphine administration in comparison to males (50%). The absolute number of PAG-RVM neurons activated by morphine was also greater in males. These data demonstrate widespread disinhibition of PAG neurons following morphine administration. The greater morphine-induced activation of PAG output neurons in male compared with female rats is consistent with the greater morphine-induced antinociception observed in males.

Comparison of angioscopy, intravascular ultrasound imaging and quantitative coronary angiography in predicting clinical outcome after coronary intervention in high risk patients.

OBJECTIVES: The purpose of this study was to identify qualitative or quantitative variables present on angioscopy, intravascular ultrasound imaging or quantitative coronary arteriography that were associated with adverse clinical outcome after coronary intervention in high risk patients. BACKGROUND: Patients with acute coronary syndromes and complex lesion morphology on angiography are at increased risk for acute complications after coronary angioplasty. Newer devices that primarily remove atheroma have not improved outcome over that of balloon angioplasty. Intravascular imaging can accurately identify intraluminal and intramural histopathologic features not adequately visualized during coronary arteriography and may provide mechanistic insight into the pathogenesis of abrupt closure and restenosis. METHODS: Sixty high risk patients with unstable coronary syndromes and complex lesions on angiography underwent angioscopy (n = 40) and intravascular ultrasound imaging (n = 46) during interventional procedures. In 26 patients, both angioscopy and intravascular ultrasound were performed in the same lesion. All patients underwent off-line quantitative coronary arteriography. Coronary interventions included balloon (n = 21) and excimer laser (n = 4) angioplasty, directional (n = 19) and rotational (n = 6) atherectomy and stent implantation (n = 11). Patients were followed up for 1 year for objective evidence for recurrent ischemia. RESULTS: Patients whose clinical presentation included rest angina or acute myocardial infarction or who received thrombolytic therapy within 24 h of procedure were significantly more likely to experience recurrent ischemia after intervention. Plaque rupture or thrombus on preprocedure angioscopy or angioscopic thrombus after intervention were also significantly associated with adverse outcome. Qualitative or quantitative variables on angiography, intravascular ultrasound or off-line quantitative arteriography were not associated with recurrent ischemia on univariate analysis. Multivariate predictors of recurrent ischemia were plaque rupture on preprocedure angioscopy (p < 0.05, odds ratio [OR] 10.15) and angioscopic thrombus after intervention (p < 0.05, OR 7.26). CONCLUSIONS: Angioscopic plaque rupture and thrombus were independently associated with adverse outcome in patients with complex lesions after interventional procedures. These features were not identified by either angiography or intravascular ultrasound.

A family study of sex differences in the diagnosis of atypical schizophrenia.

It has been hypothesized that women are more likely than men to have atypical schizophrenia. Among 984 relatives of patients with typical and atypical schizophrenia, the odds of having atypical schizophrenia did not differ by sex.

Brain SPECT and the effect of cerebral angioplasty in delayed ischemia due to vasospasm.

Cerebral vasospasm is a major determinant of outcome after subarachnoid hemorrhage (SAH). Brain SPECT with 99mTc-HMPAO was obtained before and after cerebral angioplasty in 10 patients with delayed ischemia due to vasospasm. Eight patients had clinically evident neurologic improvement after the procedure. Visual interpretation and an internal-reference (cerebellum), manual, semi-quantitative region of interest (ROI) analysis revealed improvement of regional cerebral blood flow (rCBF) in 9 out of 10. There were disagreements between the visual and ROI analysis in the two that did not improve clinically. For all 10, the average increase per anterior circulation vessel dilated (n = 17) was 8.8% by comparison of the corticocerebellar ratios. For the eight that improved, the average increase was 10.5%. Brain SPECT is valuable for evaluating delayed cerebral ischemia caused by vasospasm after SAH and is useful to document the changes in rCBF induced by angioplasty. It is possible that SPECT may be useful to detect critical reductions in perfusion before clinical deficits develop, thereby offering the potential to identify candidates for early treatment with angioplasty.

Analysis of different methods of assessing the stenotic mitral valve area with emphasis on the pressure gradient half-time concept.

There are 2 different theoretical models that analyze factors influencing the transmitral pressure gradient half-time (T1/2), defined as the time needed for the pressure gradient to reach half its initial value. In this report the models and the assumptions inherent in them were summarized. One model includes left heart chamber compliance, the other does not. Although the models at a superficial glance seem to be contradictory, the conclusions drawn from them are similar: i.e., T1/2 is influenced not only by valve area, but also by initial maximal pressure gradient and by flow. Different clinical situations in which the T1/2 method for valve area estimation has been shown not to work are analyzed in the 2 models. It is concluded that these models have contributed to our understanding of the T1/2 concept and when it should not be used. We also advocate use of the continuity equation in these situations, since no assumptions then need be made.

Disability and welfare--who wants it?

Over 4 million people under the age of 65 currently receive Social Security Disability Insurance (DI) benefits or Supplemental Security Income (SSI). Research on these groups is limited. The charts of 284 patients referred for psychiatric evaluation by Disability Determination were examined. Of this group, 148 (52%) were psychotic: 61 (41%) had schizophrenia, 37 (25%) depression, 27 (18%) undiagnosed psychosis, and 23 (16%) mania. Chronic medical illness was present in 27 (73%) of the depressives, but only 9 (8%) of the other three groups. Implications of these findings are discussed.

A snake lady: post-concussion syndrome manifesting visual hallucinations of snakes.

A 37-year-old female was referred to the Department of Psychiatry at the University of Iowa with visual hallucinations of snakes that began ten months after a brief loss of consciousness in a car accident. She also complained about a persistent headache and depressed mood that began shortly after the accident. Her depressive symptoms did not respond to amitriptyline or ECT. By thoroughly reviewing the clinical features and course of this patient, we conclude that the she did not have a typical, definite psychiatric syndrome explaining her hallucinations. The hallucination of snakes in this case may be a manifestation of post-concussional syndrome.

A study of a family with leopard syndrome.

We report a family with multiple lentigines syndrome and a manic-like psychosis. The psychosis and multiple lentigines syndrome are genetically unrelated, since the psychosis occurred in a maternal half-sibling of the propositus, while multiple lentigines syndrome occurred in the father of the propositus. The propositus also had Gilbert's syndrome and mitral valve prolapse. No other family members personally examined had either of these last two disorders.

Pressure half-time does not always predict mitral valve area correctly.

A theory is presented elucidating factors that influence the pressure half-time. By combining the Bernoulli and continuity equations and making certain assumptions about the shape of the atrioventricular pressure difference decay, it can be shown that valve area, volume transported across that area, and initial pressure difference influence the pressure half-time according to a formula in which the pressure half-time is related to V/(Ao square root of delta po), where V is the transported volume across the orifice with the area Ao, and delta po is the initial pressure difference across that area. In a subsequent hydraulic model experiment pressure half-time was determined for three different hole areas, with various initial volumes and initial pressure gradients. We did not obtain a unique relation between the pressure half-time and area. Instead the results supported our theory, and we found a close linear relationship between area and V/(T0.5 square root of delta po) (correlation coefficient [r] = 0.998), as predicted in the theory (T0.5 = pressure half-time). Clinical examples in which the pressure half-time may be misleading in the assessment of severity of mitral stenosis are presented.

Determination of regurgitant flow and volume by integrating actual proximal velocities over hemispheres (IPROV) in two orthogonal planes.

The proximal acceleration technique is a promising technique for quantification of regurgitant valve flow. Although the shape of the regurgitant proximal isovelocity field has been shown to vary with orifice size, geometry, and driving pressure, normally the centerline velocity alone is used for estimation of flow. In this model study of pulsatile flow, two-dimensional and spectral Doppler data were transferred digitally to a computer in which proximal velocity fields were corrected for time and angle errors. With the purpose of improving accuracy, flow was estimated by integrating proximal velocities over nonisovelocity spheric control surfaces in the best zone of measurement (0.15 to 0.45 m/sec at an angle up to +/- 45 degrees from the center line) in two perpendicular planes. Three regurgitant volumes in the range of 5 to 21 ml were studied for circular (diameters of 4, 6, and 8 mm), crescent, and diagonal orifices. The quotient between effective orifice area, estimated by dividing peak flow with peak velocity in the vena contracta, and true orifice area (Aeff = Q(tm)/Vo(tm)) was 0.66 (range 0.60 to 0.79), 0.50 (0.48 to 0.52), and 0.67 (0.66 to 0.68) for the circular, crescent, and diagonal orifices, respectively. Regurgitant volume estimated by multiplying effective orifice area by the velocity-time integral in the vena contracta (V = Aeff.velocity-time integral) ranged from 92% to 115% of the true volume for the circular, 89% to 92% for the crescent, and 105% to 112% for the diagonal orifices, respectively. It is possible to calculate regurgitant volume correctly with data acquisition from multiple hemispheres and planes and postprocessing of data. This amendment of the proximal acceleration technique has great advantage over the center-line method, especially when the orifice is asymmetric.

Two-dimensional color Doppler flow velocity profiles can be time corrected with an external ECG-delay device.

Although two-dimensional ultrasound color flow imaging is often considered to be a real-time technique, the acquisition time for two-dimensional color images may be up to 200 msec. Time correction is therefore necessary to obtain correct flow velocity profiles. We have developed a time-correction method in which a specially designed unit detects the QRS complex from the patient and creates a trig pulse that is delayed incrementally in relation to the QRS complex. This trig pulse controls the acquisition of the ultrasound images. A number of consecutively delayed images, with known incremental delay between the sweeps, can thus be stored in the memory of the echocardiograph and transferred digitally to a computer. The time-corrected flow velocity profile is obtained by interpolation of data from the time-delayed profiles. The system was evaluated in a Doppler string phantom test. With this technique it is possible to study time-corrected flow velocity profiles without the need to alter existing ultrasound Doppler equipment.

Subaortic flow profiles in aortic valve disease: a two-dimensional color Doppler study.

With time-corrected color Doppler echocardiography, the aortic subvalvular spatial flow velocity profile was registered in two perpendicular planes in 10 patients with aortic valve disease and in 5 healthy control subjects. Patients with predominant aortic valve stenosis had a fairly flat profile, and the subvalvular diameter, obtained from left parasternal two-dimensional tissue imaging, provided a good estimate of the mean of the two transverse flow axes. This explains the accuracy in determination of stroke volume and aortic valve area that is reported in studies on patients with aortic valve stenosis when the continuity equation is used. However, the use of apical pulsed Doppler ultrasound registrations from the left ventricular outflow tract and parasternal two-dimensional echocardiography for flow area calculation may introduce large errors in calculated stroke volume in certain patients with aortic regurgitation and in normal subjects, because of a non-flat spatial velocity profile or an inaccurate estimate of flow area.

Understanding continuous-wave Doppler signal intensity as a measure of regurgitant severity.

Continuous-wave Doppler signal intensity is commonly expected to reflect the severity of mitral regurgitation. Physical principles predict that alignment of the imaging beam, flow velocity, and turbulence can also be important or even dominant determinants of continuous-wave Doppler signal intensity. The reliability of tracking regurgitant severity with continuous-wave Doppler signal intensity was assessed in vitro with varying volume, velocity, turbulence, and beam alignment. The conditions wherein continuous-wave Doppler signal intensity increased with regurgitant volume were specific but poorly predictable combinations of orifice size, flow volume, and perfect beam alignment. Under other conditions flow velocity and turbulence effects dominated, and continuous-wave Doppler signal intensity did not reflect changing regurgitant volume. Continuous-wave Doppler signal intensity-based impressions of regurgitant severity may be unreliable and even misleading under some circumstances.

Estimation of volume flow rate by surface integration of velocity vectors from color Doppler images.

A new Doppler echocardiographically based method has been developed to quantify volume flow rate by surface integration of velocity vectors (SIVV). Electrocardiographic-gated color Doppler images acquired in two orthogonal planes were used to estimate volume flow rate through a bowl-shaped surface at a given time and distance from the probe. To provide in vitro validation, the method was tested in a hydraulic model representing a pulsatile flow system with a restrictive orifice. Accurate estimates of stroke volume (+/- 10%) were obtained in a window between 1.2 and 1.6 cm proximal to the orifice, just before the region of prestenotic acceleration. By use of the Bernoulli's equation, the estimated flows were used to generate pressure gradient waveforms across the orifice, which agreed well with the measured flows. To demonstrate in vivo applicability, the SIVV method was applied retrospectively to the determination of stroke volume and subaortic flow from the apical three-chamber and five-chamber views in two patients. Stroke volume estimates along the left ventricular outflow tract showed a characteristic similar to that in the in vitro study and agreed well with those obtained by the Fick oxygen method. The region where accurate measurements can be obtained is affected by instrumental factors including Nyquist velocity limit, wall motion filter cutoff, and color flow sector angle. The SIVV principle should be useful for quantitative assessment of the severity of valvular abnormalities and noninvasive measurement of pulsatile volume flows in general.

Problems in timing of respiration with the nasal thermistor technique.

When one analyzes transvalvular and venous flow velocity patterns, it is important to relate them to respiration. For this reason a nasal thermistor technique is often used, although it is known that this signal is delayed in relation to intrathoracic pressure changes. The magnitude and variation in delay have not been investigated previously and were, therefore, studied in a model experiment in 10 normal subjects, in 10 patients with obstructive, and in 10 patients with restrictive pulmonary disease. Esophageal pressure variations measured with an air-filled balloon served as a gold standard for intrathoracic pressure changes. During basal conditions there was, for both patient groups and normal subjects, a considerable delay of the thermistor signal. The average delay for all subjects was 370 msec with a wide variation (from 120 to 720 msec). At higher breathing frequencies the delay shortened to 310 msec (P < 0.01) but there was still a wide variation (ranging from 200 to 470 msec). Theoretic calculations show that the delay caused by the respiratory system accounts for only a minor portion of the total delay. Model experiments confirmed that the response characteristics of the thermistor probes limit the accuracy in timing of respiration. The total delay with the investigated thermistor technique is too long and variable to fulfil clinical demands.

The shape of the proximal isovelocity surface area varies with regurgitant orifice size and distance from orifice: computer simulation and model experiments with color M-mode technique.

The hemispheric proximal isovelocity surface area method for quantification of mitral regurgitant flow (i.e., Qc = 2 pi r2v), where 2 pi r2 is the surface area and v is the velocity at radius r, was investigated as distance from the orifice was increased. Computer simulations and steady flow model experiments were performed for orifices of 4, 6, and 8 mm. Flow rates derived from the centerline velocity and hemispheric assumption were compared with true flow rates. Proximal isovelocity surface area shape varied as distance from each orifice was increased and could only be approximated from the hemispheric equation when a certain distance was exceeded: > 7, > 10, and > 12 mm for the 4, 6, and 8 mm orifices, respectively. Prediction of relative error showed that the best radial zone at which to make measurements was 5 to 9, 6 to 14 and 7 to 17 mm for the 4, 6, and 8 mm orifices, respectively. Although effects of a nonhemispheric shape could be compensated for by use of a correction factor, a radius of 8 to 9 mm can be recommended without the use of a correction factor over all orifices studied if a deviation in calculated as compared with true flow of 15% is considered acceptable. These measurements therefore have implications for the technique in clinical practice.

Duration criteria and long-term outcome in affective disorder and schizophrenia.

This paper attempts to see whether the shorter duration criteria for affective disorders may naturally result in selecting patients who would show a better long-term outcome than that of schizophrenic patients. Follow-up of 298 patients with mania or depression revealed that those with 6 months or more of symptoms still had a better outcome than the outcome of schizophrenics. Furthermore, their outcome was similar to that of manics and depressives with less than 6 months of symptoms. Therefore, factors other than the shorter duration criterion for affective disorders should be sought to explain their better outcome than that of schizophrenics.

Heat transfer evaluation of the nasal thermistor technique.

When analyzing transvalvular and venous flow velocity patterns, it is important to relate them to respiration. An accurate recording of respiratory phase can be carried out with different methods. One of these methods is the use of a thermistor, which reacts to the variation in air temperature, placed in the noise of the patient. The thermistor used has a diameter for 1.0 mm and is of standard bead type. Although small, it has a considerable long time-constant and a long time-delay. The high time-constant gives a low cutoff frequency, well below the respiratory frequency and thereby causing a large phase difference. The thermistor was analyzed with the lumped heat capacity method, where it was easy to study the influence from design parameters, time-dependent air temperature, and velocity. The analysis was extended using the finite element method and the temperature field in the thermistor and the probe was calculated as a function of space and time. These calculations confirmed the result from the lumped model. The result showed that timing of respiration was not accurately obtained with the thermistor analyzed. To improve the timing, it was necessary either to change the measuring method or to use signal processing in order to achieve faster response.

Bio-acoustic signals from stenotic tube flow: state of the art and perspectives for future methodological development.

To study the degree of stenosis from the acoustic signal generated by the turbulent flow in a stenotic vessel, so-called phonoangiography was first suggested over 20 years ago. A reason for the limited use of the technique today may be that, in the early work, the theory of how to relate the spectrum of the acoustic signal to the degree of the stenosis was not clear. However, during the last decade, the theoretical basis for this and other biological tube flow applications has been clarified. Now there is also easy access to computers for frequency analysis. A further explanation for the limited diagnostic use of bio-acoustic techniques for tube flow is the strong competition from ultrasound Doppler techniques. In the future, however, applications may be expected in biological tube flow where the non-invasive, simple and inexpensive bio-acoustic techniques will have a definite role as a diagnostic method.