Endogenous motion of liver correlates to the severity of portal hypertension

BACKGROUND Degree of portal hypertension(PH) is the most important prognostic factor for the decompensation of liver cirrhosis and death, therefore adequate care for patients with liver cirrhosis requires timely detection and evaluation of the presence of clinically significant PH(CSPH) and severe PH(SPH). As the most accurate method for the assessment of PH is an invasive direct measurement of hepatic venous pressure gradient(HVPG), the search for non-invasive methods to diagnose these conditions is actively ongoing.AIM To evaluate the feasibility of parameters of endogenously induced displacements and strain of liver to assess degree of PH.METHODS Of 36 patients with liver cirrhosis and measured HVPG were included in the casecontrol study. Endogenous motion of the liver was characterized by derived parameters of region average tissue displacement signal(dantero, dretro, d RMS) and results of endogenous tissue strain imaging using specific radiofrequency signal processing algorithm. Average endogenous strain μ and standard deviation σ of strain were assessed in the regions of interest(ROI)(1 cm × 1 cm and 2 cm × 2 cm in size) and different frequency subbands of endogenous motion(0-10 Hz and 10-20 Hz).RESULTS Four parameters showed statistically significant(P 0.05) correlation with HVPG measurement. The strongest correlation was obtained for the standard deviation of strain(estimated at 0-10 Hz and 2 cm × 2 cm ROI size). Three parameters showed statistically significant differences between patient groups with CSPH, but only dretro showed significant results in SPH analysis. According to ROC analysis area under the curve(AUC) of the σROI[0…10 Hz, 2 cm × 2 cm] parameter reached 0.71(P = 0.036) for the diagnosis of CSPH; with a cut-off value of 1.28 μm/cm providing 73% sensitivity and 70% specificity. AUC for the diagnosis of CSPH for μROI[0…10 Hz, 1 cm × 1 cm] was 0.78(P = 0.0024); with a cut-off value of 3.92 μm/cm providing 73% sensitivity and 80% specificity. Dretro parameter had an AUC of 0.86(P = 0.0001) for the diagnosis of CSPH and 0.84(P = 0.0001) for the diagnosis of SPH. A cut-off value of-132.34 μm yielded 100% sensitivity for both conditions, whereas specificity was 80% and 72% for CSPH and SPH respectively.CONCLUSION The parameters of endogenously induced displacements and strain of the liver correlated with HVPG and might be used for non-invasive diagnosis of PH.     

The precision of positron emission tomography: theory and measurement

The limits of quantitation with positron emission tomography (PET) are examined with respect to the noise propagation resulting from radioactive decay and other sources of random error. Theoretical methods for evaluating the statistical error have been devised but seldom applied to experimental data obtained on human subjects. This paper extends the analysis in several ways: (1) A Monte Carlo method is described for tracking the propagation of statistical error through the analysis of in vivo measurements; (2) Experimental data, obtained in phantoms, validating the Monte Carlo method and other methods are presented; (3) A difference in activation paradigm, performed on regional CBF (rCBF) data from five human subjects, was analyzed on 1.6-cm diameter regions of interest to determine the mean fractional statistical error in PET tissue concentration and in rCBF before and after stereotactic transformation; and (4) A linear statistical model and calculations of the various statistical errors were used to estimate the magnitude of the subject-specific fluctuations under various conditions. In this specific example, the root mean squared (RMS) noise in flow measurements was about three times higher than the RMS noise in the concentration measurements. In addition, the total random error was almost equally partitioned between statistical error and random fluctuations due to all other sources.     

The 5-year results of a randomized trial of adjuvant radiation therapy after chemotherapy in breast cancer patients treated with mastectomy

The use of adjuvant radiation therapy in breast cancer patients treated with mastectomy and adjuvant chemotherapy has been controversial. In order to assess the necessity and effectiveness of adjuvant radiation therapy in this setting, we reviewed the results in 510 patients with T1-T3 tumors and pathologically positive nodes or tumors larger than 5 cm and negative nodes who were treated with adjuvant chemotherapy. Patients with four or more positive nodes or at least one positive apical node were randomized to receive either five or ten cycles of cyclophosphamide/Adriamycin (Adria Laboratories, Columbus, OH) (CA) and patients with one to three positive nodes or operable tumors larger than 5 cm and pathologically negative nodes were randomized to receive eight cycles of either cyclophosphamide, methotrexate, and 5-fluorouracil (5-FU) (CMF) or methotrexate and 5-FU (MF) chemotherapy. Two hundred six of these patients were subsequently rerandomized to receive either no further treatment or adjuvant radiotherapy. Thirty-five patients withdrew after randomization, including 34 who declined to receive radiotherapy. Radiation therapy consisted of 4,500 cGy in 5 weeks to the chest wall and appropriate draining lymph nodes. Median follow-up from chemotherapy randomization is 45 months for patients in the CA arm and 53 months for those in the CMF/MF arm. The crude rate of local failure (chest wall or draining lymph node areas) as first site of failure for patients randomized to receive chemotherapy only was 14%; for those randomized to receive both chemotherapy and radiotherapy it was 5% (P = .03). For patients in the CMF/MF arm, the rate of local failure as the first site of failure was nearly the same for patients randomized to chemotherapy only as for those randomized to adjuvant radiotherapy as well (5% v 2%). For patients in the CA arm, the crude rate of local failure was 20% for patients randomized to receive chemotherapy only, and 6% for those randomized to both types of adjuvant treatment (P = .03). Among the 43 patients treated with CA who actually received radiotherapy, there was only one local failure, compared with 12 local failures among the 59 patients (20%) who actually did not receive radiotherapy (P = .007). No significant difference was seen in disease-free survival or overall survival in either the CA or the CMF/MF arm between patients randomized to receive radiation therapy and those randomized to no further treatment.(ABSTRACT TRUNCATED AT 400 WORDS)     

Plus disease in retinopathy of prematurity: pilot study of computer-based and expert diagnosis.

PURPOSE: To measure accuracy of plus disease diagnosis by recognized experts in retinopathy of prematurity (ROP), and to conduct a pilot study examining performance of a computer-based image analysis system, Retinal Image multiScale Analysis (RISA). METHODS: Twenty-two ROP experts independently interpreted a set of 34 wide-angle retinal images for presence of plus disease. A reference standard diagnosis based on expert consensus was defined for each image. Images were analyzed by the computer-based system using individual and linear combinations of system parameters for arterioles and venules: integrated curvature (IC), diameter, and tortuosity index (TI). Sensitivity, specificity, and receiver operating characteristic areas under the curve (AUC) for plus disease diagnosis compared with the reference standard were determined for each expert, as well as for the computer-based system. RESULTS: Expert sensitivity ranged from 0.308 to 1.000, specificity ranged from 0.571 to 1.000, and AUC ranged from 0.784 to 1.000. Among individual computer system parameters, venular IC had highest AUC (0.853). Among all computer system parameters, the linear combination of arteriolar IC, arteriolar TI, venular IC, venular diameter, and venular TI had highest AUC (0.967), which was greater than that of 18 (81.8%) of 22 experts. CONCLUSIONS: Accuracy of ROP experts for plus disease diagnosis is imperfect. A computer-based image analysis system has potential to diagnose plus disease with high accuracy. Further research involving RISA system parameter cut-off values from this study are required to fully validate performance of this computer-based system compared with that of human experts.     

Larger urethral catheter size leads to fossa navicularis stricture formation in robotic radical prostatectomy

Fossa navicularis strictures following radical prostatectomy are reported infrequently. We recently experienced a series of fossa strictures following robotic-assisted laparoscopic prostatectomy (RLP). We describe herein our experience to prevent fossa strictures and to determine its etiologic factors. From June 2002 to May 2006, 424 patients underwent robotic-assisted laparoscopic prostatectomy with the da Vinci surgical system. Fossa strictures were diagnosed based on the acute onset of obstructive voiding symptoms and bougie calibration. During our series, we switched from the intra-operative use of an 18 French (F) catheter to that of a 22 F one to avoid inadvertent stapling of the urethra when dividing the dorsal venous complex. After we observed a high incidence of fossa strictures, we reverted back to 18 F catheters during surgery. All patients had an 18 F catheter indwelling for 1 week after surgery. Parameters were evaluated using Fisher’s exact test and Student’s t-test for means. The 18 F catheter group of patients (n = 293) developed one fossa stricture, whereas the 22 F catheter group (n = 131) developed nine fossa strictures (P < 0.01). The fossa stricture rate in the 18 F group was 0.3% versus 6.9% in the 22 F group. The two groups had no differences in age, body mass index, cardiovascular disease, American Urological Association symptom score, urinary bother score, preoperative prostate-specific antigen, operative time, estimated blood loss, cautery use, prostate size, or catheterization time. Based on these results, a larger urethral catheter size – 20 F versus 18 F – during the intra-operative dissection would appear to increase the risk for fossa stricture by more than 20-fold. Statement of disclosure Dr. Thomas Ahlering is a meeting participant and lecturer for Intuitive Surgical Corp. The other authors have no direct or indirect commercial financial incentives associated with publishing the article. No research or project support funding was received.     

Population toxicokinetics of tetrachloroethylene

 In assessing the distribution and metabolism of toxic compounds in the body, measurements are not always feasible for ethical or technical reasons. Computer modeling offers a reasonable alternative, but the variability and complexity of biological systems pose unique challenges in model building and adjustment. Recent tools from population pharmacokinetics, Bayesian statistical inference, and physiological modeling can be brought together to solve these problems. As an example, we modeled the distribution and metabolism of tetrachloroethylene (PERC) in humans. We derive statistical distributions for the parameters of a physiological model of PERC, on the basis of data from Monster et al. (1979). The model adequately fits both prior physiological information and experimental data. An estimate of the relationship between PERC exposure and fraction metabolized is obtained. Our median population estimate for the fraction of inhaled tetrachloroethylene that is metabolized, at exposure levels exceeding current occupational standards, is 1.5% [95% confidence interval (0.52%, 4.1%)]. At levels approaching ambient inhalation exposure (0.001 ppm), the median estimate of the fraction metabolized is much higher, at 36% [95% confidence interval (15%, 58%)]. This disproportionality should be taken into account when deriving safe exposure limits for tetrachloroethylene and deserves to be verified by further experiments. Received: 20 April 1995/Accepted: 24 August 1995     

Retention of "safe" blood donors. The Retrovirus Epidemiology Donor Study

BACKGROUND: There are obvious advantages to increasing donor retention. However, for reasons of blood safety, certain donors may, in fact, be more desirable to retain than others. “Safe” donors are defined as those who provided a blood donation that was negative on all laboratory screening tests and who subsequently reported no behavioral risks in response to an anonymous survey. This study identifies the most important factors affecting the intention of “safe” donors to provide another donation. STUDY DESIGN AND METHODS: An anonymous survey asking about donation history, sexual history, injecting drug use, and recent donation experience was mailed to 50,162 randomly selected allogeneic donors (including directed donors) who gave blood from April through July or from October through December 1993 at one of the five United States blood centers participating in the Retrovirus Epidemiology Donor Study. Before mailing, questionnaires were coded to designate donors with nonreactive laboratory screening tests at their most recent donation. RESULTS: A total of 34,726 donors (69%) responded, with substantially higher response among repeat donors. According to reported intentions only, the vast majority of “safe” donors indicated a high likelihood of donating again within the next 12 months. Only 3.4 percent reported a low likelihood of donating again. A comparison of those likely to return and those unlikely to return reveals significant differences in demographics and in ratings of the donation experience. A higher proportion of those unlikely to return were first-time donors, minority-group donors, and donors with less education. The highest projected loss among “safe” donors was seen for those who gave a fair to poor assessment of their treatment by blood center staff or of their physical well-being during or after donating. CONCLUSION: These data suggest that efforts to improve donors' perceptions of their donation experience, as well as attention to the physical effects of blood donation, may aid in the retention of both repeat and first-time donors.     

Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.     

Indomethacin increases the effect of isosorbide dinitrate on cerebral hemodynamic in migraine patients: pathogenetic and therapeutic implications

Intracerebral vascular reactivity induced by the nitric oxide (NO) donor isosorbide dinitrate (IDN, 5 mg sublingually) is more major and longer-lasting in migraine patients who develop delayed headache in response to the drug. The headache is purportedly due to neuronally-mediated vascular mechanisms. Indomethacin inhibits prostaglandin synthesis, which is involved in NO generation. Indomethacin also decreases cerebral blood flow by constricting precapillary resistance vessels. In the present study, the hemodynamic effects of indomethacin were evaluated in migraine patients and healthy controls by means of transcranial Doppler monitoring. Indomethacin caused a significant decrease in mean flow velocity in the middle cerebral artery. This was an additional effect to the mean velocity decrease induced by IDN. The interactions between the two drugs suggest that their effects on cerebral hemodynamics (and pain) may be of relevance both in understanding the role of NO in migraine pathogenesis and in evaluating symptomatic treatments for migraine attacks.