Mathematical model of liver regeneration in human live donors.

Liver regeneration after injury occurs in many mammals. Rat liver regenerates after partial hepatectomy over a period of 2 weeks while human liver regeneration takes several months. Notwithstanding this enormous difference in time-scales, with new data from five human live liver transplant donors, we show that a mathematical model of rat liver regeneration can be transferred to human, with all biochemical interactions and signaling unchanged. Only six phenomenological parameters need change, and three of these parameter changes are rescalings of rate constants by the ratio of human lifespan to rat lifespan. Data from three donor subjects with approximately equal resections were used to fit the three parameters and the data from the other two donor subjects was used to independently verify the fit.

Developmental changes in the rat atriopeptin hormonal system.

We undertook a study of fetal synthesis, storage, and release of atriopeptin (AP). Plasma levels of both atriopeptin immunoreactivity (APir) and the NH2-terminal fragment of the prohormone immunoreactivity (NTFir) were very high in the fetus (4 and 20 times the maternal plasma, respectively). However, the atrial content of the AP was low, but surprisingly, ventricular content of AP was quite high (relative to the adult) in the fetus and fell postnatally. Atrial AP messenger RNA (mRNA) increased with postnatal age, whereas ventricular mRNA was extremely high in the fetus and fell rapidly after birth. High fetal plasma peptide levels may derive from the mother since infusion of exogenous atriopeptin 24 into the mother resulted in parallel increases in fetal and maternal peptide levels. Fetal plasma APir and NTFir levels partially reflect the markedly reduced total renal metabolic capacity compared with that of the adult. Plasma levels fell progressively after birth; whereas neonatal atrial content rose substantially. Plasma AP and NTF were simultaneously elevated in both the maternal and fetal circulation after vasopressin injection of the mother. The fetus can also respond to exogenous stimuli (vasopressin or indomethacin--presumably via ductal closure) and promptly release substantial amounts of peptide into its circulation. Thus, it appears that the AP hormonal system is functional during fetal life and responds avidly to increases in intracardiac pressure as does the mature animal.

Identification and localization of multiple classic cadherins in developing rat limbic system.

Classic cadherins are multifunctional adhesion proteins that play roles in tissue histogenesis, neural differentiation, neurite outgrowth and synapse formation. Several lines of evidence suggest that classic cadherins may establish regional or laminar recognition cues by virtue of their differential expression and tight, and principally homophilic, cell adhesion. As a first step toward investigating the role this family plays in generating limbic system connectivity, we used RT-PCR to amplify type I and type II classic cadherins present in rat hippocampus during the principal period of synaptogenesis. We identified nine different cadherins, one of which, cadherin-9, is novel in hippocampus. Using in situ hybridization, we compared the cellular and regional distribution of five of the cadherins (N, 6, 8, 9 and 10) during the first two postnatal weeks in hippocampus, subiculum, entorhinal cortex, cingulate cortex, anterior thalamus, hypothalamus and amygdala. We find that each cadherin is differentially distributed in distinct, but highly overlapping fields that largely correspond to known anatomical boundaries and are often coordinately expressed in interconnected regions. For example, cadherin-6 expression defines CA1 and its principal target, the subiculum; cadherin-10 is differentially expressed in CA1 and CA3 in a manner correlating with the organization of interconnecting Schaffer collateral axons; and cadherin-9 shows a striking concentration in CA3. Some cadherin mRNAs are highly restricted to particular anatomical fields over the entire time course, while others are more broadly expressed and become concentrated within particular domains coincident with the timing of afferent ingrowth. Our data indicate that classic cadherins are sufficiently diverse and differentially distributed to support a role in cell surface recognition and adhesion during the formation of limbic system connectivity.

The role of preoperative radial artery ultrasound and digital plethysmography prior to coronary artery bypass grafting.

OBJECTIVE: Doppler ultrasound and digital plethysmography are used at our institution to determine the suitability of the radial artery for harvest prior to coronary artery bypass grafting (CABG). The purpose of this study is to determine the value of this preoperative evaluation. METHODS: A retrospective analysis of non-invasive radial artery testing was performed on 187 CABG patients. Criteria used to exclude radial arteries from harvest were anatomic abnormalities (size<2 mm, diffuse calcifications), and perfusion deficits during radial artery occlusion (>40% reduction in digital pressure, non-reversal of radial artery flow, or minimal increase in ulnar velocity). A questionnaire was used to determine the incidence of postoperative hand ischemia or rehabilitation. RESULTS: In 187 patients, 346 arms were evaluated. Ninety-four arms (27.1%) were excluded for harvesting. Anatomical abnormalities included size<2 mm (1.5%), diffuse calcifications (8.7%), congenital anomalies (2.3%), and radial artery occlusion (0.3%). Circulatory abnormalities included non-reversal of flow (7.2%), abnormal digital pressures (5.5%), and inappropriate increase in ulnar velocity (1.7%). A total of 116 radial arteries were harvested. There were no episodes of hand ischemia. No patient required hand rehabilitation. CONCLUSIONS Doppler ultrasound and digital plethysmography identifies both perfusion (14.5%) and anatomical (12.7%) abnormalities that may make the radial artery less suitable as a bypass conduit.

Pressure dependence of subharmonic signals from contrast microbubbles.

Noninvasive pressure estimation in heart cavities and in major vessels would provide clinicians with a valuable tool for assessing patients with heart and vascular diseases. Some microbubble-based ultrasound contrast agents are particularly well suited for pressure measurements because their substantial compressibility enables microbubbles to vary significantly in size in response to changes in pressure. Pressure changes should then affect reflectivity of microbubbles after intravenous injection of a contrast agent. This has been demonstrated with a galactose-based contrast agent using 2.0-MHz ultrasound tone bursts. Preliminary results indicate that, over the pressure range of 0-186 mmHg, the subharmonic amplitude of scattered signals decreases by as much as 10 dB under optimal acoustic settings and the first and second harmonic amplitudes decrease by less than 3 dB. An excellent correlation between the subharmonic amplitude and the hydrostatic pressure suggests that the subharmonic signal may be utilized for noninvasive detection of pressure changes.

Anterior protrusion of retroperitoneal processes. A mimic of lesser sac or gastrohepatic masses.

The space between the left lobe of the liver and the lesser curvature of the stomach normally contains intraperitoneal structures. These include the gastrohepatic recess of the greater peritoneal cavity, the medial recess of the lesser sac and the interposed gastrohepatic ligament. An anterior protrusion of retroperitoneum can project into this space, dorsal to the posterior reflection of the medial compartment of the lesser sac. Tumors that extend into this fossa are anterior and medial to the fundic and upper body region of the stomach. These tumors may cause confusion regarding their origin if the radiologist is not aware of the existence of this retroperitoneal protrusion. Between 1982, and 1986, 183 patients with pancreatic cancer were hospitalized at our institution, 63 of whom had computed tomography (CT) scans of the abdomen. Four of these patients (6.3%) demonstrated direct tumor extension anterior to the stomach. During this same period, four large benign retroperitoneal tumors also exhibited this finding. Masses in the gastrohepatic interval between the liver and stomach can be extensions of retroperitoneal processes and should not be assumed to represent intraperitoneal involvement.

Doppler spectral estimation using time-frequency distributions.

The time-frequency distribution (TFD) of Doppler blood flow signals is usually obtained using the spectrogram, which requires signal stationarity and is known to produce large estimation variance. This paper examines four alternative, nonstationary spectral estimators: a smoothed pseudo-Wigner distribution (SPWD), the Choi-Williams distribution (CWD), the Bessel distribution (BD), and the novel, adaptive constant-Q distribution (AQD) for their applicability to Doppler ultrasound. A synthetic Doppler signal, simulating the nonaxial and pulsatile flow of the common carotid artery, was used for quantitative comparisons at different signal-to-noise-ratios (SNR) of 0, 10, 20, and 30 dB as well as noise free. The cross-correlation (rho) and the root-mean-square-error (RMSE) were calculated after log-compression for each technique and SNR relative to the theoretical distribution. The AQD consistently had the lowest RMSE (< or =53.7%) and the highest rho (> or =0.889) of all the TFDs, irrespective of the SNR. The SPWD performed better than the spectrogram, which performed better than the BD and the CWD. Qualitative comparisons were carried out using in vivo data acquired with a 10 MHz ultrasound cuff transducer positioned around the distal aorta of a rabbit. In vivo, the AQD was considered best with respect to background noise and internal gray scale features; it was rated second (after the spectrogram) in depicting the spectral envelope. The AQD performed better as a Doppler spectral estimator than the traditional spectrogram and the other TFDs under the conditions studied here.

Clinical applications of ultrasound contrast agents.

Within the last decade safe and practical ultrasound contrast agents have been introduced. Most of these are based on gas-filled microbubbles, which markedly enhance Doppler signals and, in some cases, also gray-scale images. The clinical improvements expected from ultrasound contrast is reviewed. Tissue-specific contrast agents constitute another area of potential clinical significance. One particular agent is taken up by the reticulo-endothelial system and produces so-called acoustic emission signals when imaged. An introduction to the unique clinical applications of acoustic emission is given. Harmonic imaging is a new contrast-specific imaging modality, which utilizes the nonlinear properties of some agents in an attempt to alleviate current limitations of ultrasound contrast studies. Examples of harmonic images are presented.

Breast tumor vascularity identified by contrast enhanced ultrasound and pathology: initial results.

Quantifiable measures of vascularity obtained from contrast enhanced color flow images were correlated with pathologic vascularity measurements in ten female patients with a solid breast mass. Each patient received Levovist Injection (Berlex Laboratories Inc., Montville, NJ). Color flow images pre- and post-contrast were obtained using an HDI 3000 unit (ATL, Bothell, WA) before removing the mass for pathologic vascularity assessments. Image-processing techniques were used to obtain both the ultrasound and pathologic vascularity measurements. Multiple linear regression found significant correlations for ultrasonic vascularity measurements post contrast and pathology (P = 0.02 and 0.06). No correlations were found between pre-contrast ultrasound and pathology. In conclusion, post-contrast ultrasonic flow measures provide a non-invasive measure of breast tumor neovascularity. However, the patient population is small, and until further patients are analyzed, these conclusions are preliminary.

Clinical impact of sonographically guided biopsy of salivary gland masses and surrounding lymph nodes.

Although fine-needle aspiration biopsy of salivary gland masses has been reported in the otolaryngology literature, the use of sonography to guide the biopsy of nonpalpable masses and masses seen on other cross-sectional imaging studies has not been described. Our goal was to evaluate sonographically guided biopsy of masses and lymph nodes related to the salivary glands. We analyzed the records of 18 patients who had undergone fine-needle aspiration biopsy of a salivary gland mass or lymph node with a 25-, 22-, or 20-gauge needle. A definitive cytologic diagnosis was made for 13 of the 18 patients (72%); cytology was suggestive but not definitive in three patients (17%) and insufficient in two (11%). Definitive diagnoses were made in three cases of reactive lymph node, in two cases each of lymph node metastasis and Warthin's tumor, and in one case each of pleomorphic adenoma, adenoid-cystic carcinoma, schwannoma-neurofibroma, parotid metastasis, parotid lymphoma, and Sjögren's-related lymphoid-epithelial lesion. Sonographically guided biopsy allows for confident needle placement in masses seen on computed tomography and magnetic resonance imaging. Sonography can usually distinguish a perisalivary lymph node from true intrasalivary masses, and it can help the surgeon avoid the pitfall of a nondiagnostic aspiration of the cystic component of masses. We conclude that sonographically guided biopsy of salivary gland masses can provide a tissue diagnosis that can have a direct impact on clinical decision making.

Canadian fertility trends in perspective.

PIP: This paper examines the broad movements of Canadian period and cohort fertility over the past 100 years, and compares them with corresponding trends in the US and other industrialized countries. The main movement in Canada was a decline in fertility extending from the 19th century to the present, interrupted in the 1940s and 1950s by a baby boom. Between 1871 and 1937 the total fertility rate (TFR) fell at about an average of 1.4% annually. The rate of fall in the US was similar, with the result that in the late 1930s the Canadian TFR was about 20% that of the US. The fertility boom that followed was steeper in the US than in Canada, and in the downswing that later followed, the rate of decline was similar in the 2 countries (3.4-4% annual average). But, the decline continued longer-- indeed still continues--in Canada, whereas the TFR in the US reached its lowest point in 1976. Moreover, the recent decline in fertility has been more severe in Canada than in almost any other industrialized country. The TFR relates to fertility in a single year and is highly sensitive to short-term changes in the timing of births. For the purposes of understanding and explaining long-term trends in fertility, the completed fertility rate (CFR) is a better index because it measures the ultimate family size of cohorts. Cohort fertility can be seen to fluctuate much less than does period fertility. In both the US and Canada, the peak cohorts, born in the early 1930s, had roughly the same completed fertility, and later cohorts continued to remain closely in step as the CFR fell sharply. In Canada the fall continues, though at a reduced rate, in the latest cohorts for which there is information. Apart from differences in amplitude, the dates of turning points and the shapes of the TFR and CFR curves of Canadian fertility are fairly similar. The long decline in cohort fertility is largely explained by the decrease in the proportions of families of 6 or more children. During the baby boom, for Catholics and non-Catholics alike, the proportion of ever-married women remaining childless fell by about 40%, the proportion having 2 children changed little, and the proportions having 3,4 and 5 children tended to increase substantially. The crucial difference between the 2 groups was in the proportions of women having 6 or more children. For non-Catholics, the proportion fell by over 4% from a high level. For non-Catholics, on the other hand, the proportion rose somewhat, though even after the rise, it was barely more than 1/2 the level to which the Catholic proportion had declined. Among Catholics, the effect of the massive decline in the proportion of women having 6 or more children was to swamp the effects of the increase in the proportions of women having 3, 4 and 5 children. The net effect was that fertility declined. Among non-Catholics, however, the comparable increases in the proportions of families of 3, 4 and 5 children, were not offset by any fall in the proportion of larger families, with the result that a baby boom occurred.^ieng

Doppler evaluation of the renal transplant.

Well-established roles for Doppler ultrasound assessment of renal transplants include postoperative evaluation for vascular occlusion and detection of renal artery stenosis. Doppler studies can often differentiate rejecting transplants from those that normally function. While very high Doppler indices are specific for rejection, waveforms in acute tubular necrosis may be abnormal. Mild cases of rejection may have normal waveforms. Further investigation is needed to determine the role of Doppler methods in graft dysfunction and to establish methods to improve their specificity.

Color Doppler artifact in anechoic regions.

For color Doppler imaging, several types of signal processing are employed in order to produce acceptable images of blood flow in blood vessels while suppressing color in moving solid tissue. The processing can produce an artifact in which color may arise from noise or from tissue motion and fill anechoic regions preferentially. This artifact may complicate the differentiation of areas with blood flow from anechoic regions without flow. By using four different color Doppler ultrasound units to image a tissue-equivalent phantom containing anechoic cylinders, artifactual color resulted when gain was raised sufficiently. This color was concentrated in anechoic regions of a gray-scale image that did not contain flow. In two instruments, this artifact was only observed when the transducer was vibrated, simulating tissue motion. In these instruments, the identification of low-frequency, high-amplitude Doppler signals is used to locate moving solid tissue and so suppress color in these regions. In the other two instruments, the presence of echoes within the image suppressed the assignment of color. With both types of processing, color may appear artifactually in echo-free regions without flow, such as fluid collections. Presence or absence of flow should be confirmed by Doppler spectral analysis. An understanding of the origin and appearance of artifactual color can prevent its occurrence from detracting from the usefulness of color Doppler imaging.

Portal vein pulsatility in normal and cirrhotic adults without cardiac disease.

The literature indicates that Doppler demonstration of pulsatile flow in the portal vein suggests heart disease, and that retrograde transsinusoidal transmission of atrial pulsations is the mechanism. We noninvasively investigated portal vein pulsatility (PVP) in normal subjects and in patients with cardiac and liver disease, and performed invasive studies in cirrhotic humans and normal pigs. We found that accentuated PVP occurred in some normal subjects and in some patients with cirrhosis, and that mechanisms other than transsinusoidal transmission of atrial pulsations contributed to PVP. Determinants of PVP may include pulsatile portal inflow, transmission of pulsations from the vena cava (IVC) and location of the Doppler sample volume relative to the IVC.

CT-pathologic correlation of axillary lymph nodes in breast carcinoma.

A prospective study was performed to determine whether thoracic CT yielded useful information regarding the status of axillary lymph nodes (LNs) in patients with breast cancer. Thirty-five consecutive patients with clinically suspected stage II or III breast carcinomas were scanned preoperatively from the supraclavicular regions to the lung bases. Axillary LNs measuring greater than or equal to 1 cm were considered abnormal. The lymph nodes were classified according to their relationship to the pectoralis muscle. Extracapsular lymph node extension was diagnosed when there was irregularity and spiculation of the lymph node margin with surrounding fatty infiltration. Correlation with axillary dissection was obtained in 20 patients, giving a positive predictive value for axillary metastases of 89% with 50% sensitivity, 75% specificity, and 20% negative predictive value. CT was also able to detect the level of axillary involvement accurately when the lymph nodes were enlarged and to evaluate extracapsular LN extension. Although superior to physical examination, CT was not an accurate predictor of axillary LN involvement, primarily because of its low negative predictive value.

Circle of Willis in newborns: color Doppler imaging of 53 healthy full-term infants.

To establish the usual pattern of flow in the circle of Willis in newborns, the authors scanned 53 healthy full-term infants within 3 days of birth with color Doppler imaging. All examinations were performed and images interpreted by the same experienced individuals. The basilar, internal carotid (ICA), and anterior and middle cerebral arteries were seen in all infants. Vertebral, posterior cerebral, superior cerebellar, and posterior communicating (PCoA) arteries were seen in most infants. PCoA flow was from the ICA toward the posterior cerebral artery in 73 (98.6%) of the 74 vessels that were seen. Flow in the anterior communicating artery was seen in six infants, indicating dependence of an anterior cerebral artery on contralateral ICA perfusion. Two pitfalls involving the distal portion of the ICA were noted: This vessel could be confused with the proximal portion of the anterior cerebral artery or cavernous sinus if real-time images were not interpreted carefully. Variant patterns of flow included tortuous basilar arteries (n = 2), reversed PCoA flow (n = 1), and inferior angulation of the proximal portions of the anterior cerebral arteries (n = 2). Color Doppler imaging allows a detailed analysis of the circle of Willis in newborns and detection of some anatomic variations.

Sonographic evaluation of fetal growth: growth rate variability as a function of the interval between examinations.

OBJECTIVE: Fetal growth rates determined on the basis of findings at two separate sonographic examinations can be used to detect growth abnormalities. This article determines the relationship between the length of the interval between examinations and the associated variability in measured fetal growth rates. MATERIALS AND METHODS: We analyzed 1479 fetal measurements of the biparietal diameter, average abdominal diameter, and femur length from 539 normal pregnancies. Mean growth rates were computed as functions of gestational age. The standard deviation of the growth rate was computed as a function of the interval between examinations. RESULTS: The standard deviation of fetal growth rates is relatively constant when the interval between examinations is 8-10 weeks or more, but increases substantially when the interval is fewer than 6 weeks. CONCLUSION: From a purely statistical point of view, the optimal interval for assessment of fetal growth rates is 8-10 weeks or more. Shorter intervals, however, usually are mandated by the clinical situation. Correction factors can be used to determine the standard deviations and associated confidence intervals for fetal growth measured over a period of fewer than 10 weeks.