Distinct gut and vaginal microbiota profile in women with recurrent implantation failure and unexplained infertility.

BACKGROUND: Female reproductive tract dysbiosis impacts implantation. However, whether gut dysbiosis influences implantation failure and whether it accompanies reproductive tract dysbiosis remains scantly explored. Herein, we examined the gut-vaginal microbiota axis in infertile women. METHODS: We recruited 11 fertile women as the controls, and a cohort of 20 infertile women, 10 of whom had recurrent implantation failure (RIF), and another 10 had unexplained infertility (UE). Using amplicon sequencing, which employs PCR to create sequences of DNA called amplicon, we compared the diversity, structure, and composition of faecal and vaginal bacteria of the controls with that of the infertile cohort. Of note, we could only sequence 8 vaginal samples in each group (n = 24/31). RESULT: Compared with the controls, α-diversity and ß-diversity of the gut bacteria among the infertile groups differed significantly (p < 0.05). Taxa analysis revealed enrichment of Gram-positive bacteria in the RIF group, whereas Gram-negative bacteria were relatively abundant in the UE group. Strikingly, mucus-producing genera declined in the infertile cohort (p < 0.05). Hungatella, associated with trimethylamine N-oxide (TMAO) production, were enriched in the infertile cohort (p < 0.05). Vaginal microbiota was dominated by the genus Lactobacillus, with Lactobacillus iners AB-1 being the most abundant species across the groups. Compared with the infertile cohort, overgrowth of anaerobic bacteria, associated with vaginal dysbiosis, such as Leptotrichia and Snethia, occurred in the controls. CONCLUSION: The gut microbiota had little influence on the vaginal microbiota. Gut dysbiosis and vaginal eubiosis occurred in the infertile women, whereas the opposite trend occurred in the controls.

Simulating the use of re-prioritisation as a wait-reduction strategy in an emergency department.

BACKGROUND/AIM: Simulation modelling has proven a useful approach for capturing the dynamic nature of emergency departments (EDs) and informing improvements to clinical and operational processes alike. However, few models have simulated the impact of the UK Department of Health's 4 h operational standard, which arguably has placed pressure to improve standards and performance, promoting the use of wait-reduction strategies to cope with the target in practice. The aim of this study was to determine the impact a re-prioritisation strategy has on the 4 h target by simulating the operation of an ED using a model that represents the flow of patients through the department. METHODS: This study was based on a district general hospital in West London. To ascertain patients' length of stay, the hospital's historical records and staff rotas were used to obtain data on activities, timeframes and resources on three separate representative weeks and included all patients' arrival time, mode of arrival, whether the patient was referred to minors, majors, paediatrics or the resuscitation unit, and whether the patient was admitted or discharged, and at what time. RESULTS: The close correlation (r=0.98) in distributions between actual length of stay and simulated length of stay demonstrates that the model of the ED accurately replicates the 4 h peak caused by the use of re-prioritisation. CONCLUSION: The model accurately reproduced the use of a dominant wait-reduction strategy to identify patients approaching the breach and re-prioritise them to expedite treatment and remove them from the department by the 4 h target.

The Effect of Aloe Vera Juice on Liver Enzymes and Hepatic Structure in a Healthy Population.

BACKGROUND: There have been isolated reports of Aloe vera hepatotoxicity, usually manifested by transient liver function test abnormalities. While the European Food Safety Authority has recommended that whole leaf products containing the rind of the Aloe vera plant should not be used for human oral consumption, those Aloe vera gels made of the treated plant pulp alone are considered safe for daily consumption, provided recommended quantities are not exceeded. We aimed to assess hepatic function in healthy volunteers consuming the purified plant pulp Aloe vera gel over a 60 day period. METHODS: 35 healthy volunteers consumed the maximum recommended daily dose of 2 oz (57 mL) of Aloe vera gel twice daily for a total of 60 days. The participants attended an initial baseline visit where biochemical measurements of hepatic synthetic function were obtained, and each volunteer underwent hepatic ultrasound with elastography, superb microvascular imaging and image quantification. Further visits were undertaken at days 30 and 60 to undergo the same biochemical and imaging measurements of liver function to monitor if there were any changes in the parameters measured. RESULTS: Seven volunteers failed to complete the study, citing unspecified gastrointestinal upset and/or an inability to tolerate the taste of the Aloe vera gel. None of these individuals had disturbance of biochemical or imaging parameters of hepatic function. Of the remaining 27 healthy volunteers, none had a change in either biochemical indices of liver function, or of ultrasound markers of hepatic blood flow or liver tissue elasticity after 60 days of Aloe vera gel consumption. However, there was a non-significant reduction in serum homocysteine levels as the only detectable change in the cohort. CONCLUSIONS: Despite reports of potential hepatotoxicity with some Aloe vera products, in this healthy cohort, extended consumption of purified plant-pulp Aloe vera gel did not have any detectable effects on hepatic function, blood flow or tissue elasticity.

Pelvic imaging in gestational trophoblastic neoplasia.

OBJECTIVE: To assess the accuracy of Doppler ultrasound (DU) compared with magnetic resonance imaging (MRI) in high-risk patients with gestational trophoblastic neoplasia (GTN). STUDY DESIGN: From January 2005 to October 2007, patients with proven high-risk GTN or suspicion of relapse who had both DU and MRI of the pelvis were reviewed retrospectively for tumor detection and tumor extent and vascularity. RESULTS: There were a total of 54 patients who had both DU and MRI performed; of these, 40 were first-time presentation and 14 had either residual disease not responding to chemotherapy or suspicion of recurrent GTN based on rising human chorionic gonadotropin (hCG). Extrauterine extension and extent of endometrial encroachment were better assessed on MRI than on DU in 10 of 46 patients with visible uterine lesion. CONCLUSION: MRI and DU are complementary investigations of the pelvis in patients with GTN. Tumor vascularity is better assessed on DU, tumor extension and detection are better with MRI.

31P MR spectroscopy in assessment of response to antiviral therapy for hepatitis C virus-related liver disease.

OBJECTIVE: An increase in the ratio of phosphomonoester (PME) to phosphodiester (PDE) during 31P MR spectroscopy of the liver has been observed with increasing severity of hepatitis C-related liver disease. The purpose of this study was to investigate the utility of 31P MR spectroscopy as a biomarker of response to interferon and ribavirin treatment. SUBJECTS AND METHODS: Forty-seven patients with biopsy-proven hepatitis C undergoing viral eradication treatment with interferon and ribavirin underwent hepatic 31P MR spectroscopy at 1.5 T (voxel size, 70 x 70 x 70 mm; TR, 10,000; number of signals averaged, 48). All underwent baseline imaging before treatment and repeated imaging at 6-month intervals after the start of treatment. RESULTS: All patients underwent follow-up imaging 6 months after the start of treatment; 25 patients, 12 months; and 10 patients, 18 months after the start of treatment. According to the Ishak histologic scoring system, nine patients had mild hepatitis; 30 patients, moderate to severe hepatitis; and eight patients, cirrhosis. Thirty-two patients responded to antiviral treatment. Among these patients, 25 had a decrease in PME/PDE ratio on follow-up imaging. Among responders the mean baseline PME/PDE ratio decreased from 0.27 +/- 0.02 (standard error) to 0.16 +/- 0.01 after treatment (paired Student's t test, p < 0.001). Among the 15 virologic nonresponders, the ratios were similar in six patients; six other patients had an increase on follow-up imaging. In the latter nonresponder group, the mean baseline PME/PDE ratio was 0.21 +/- 0.03 compared with 0.31 +/- 0.08 after treatment (paired Student's t test, p =0.24). CONCLUSION: The in vivo hepatic PME/PDE ratio decreased in patients with hepatitis C who responded to antiviral treatment and remained similar or increased in patients without a virologic response. These results suggest that PME and PDE can be used as biomarkers in a noninvasive test of response to treatment.

Acute respiratory tract infection visits of veterans with spinal cord injuries and disorders: rates, trends, and risk factors.

BACKGROUND/OBJECTIVES: Respiratory complications are a major cause of illness and death in persons with spinal cord injuries and dysfunction (SCI&Ds). The objectives of this study were to examine rates of outpatient visits over 5 years for acute respiratory tract infections (ARIs), including pneumonia and influenza (P&I), lower respiratory tract infections (LRIs), and upper respiratory tract infections (URIs), in veterans with SCI&Ds and to determine whether individual characteristics were associated with the number of annual visits for each type of ARI. METHODS: This was a longitudinal (fiscal years 1998-2002) study of ARI visits at the Veterans Health Administration (VA) in 18,693 veterans with SCI&Ds. To examine the associations between time, patient characteristics, and annual number of ARI visits, we used random effect negative binomial models. RESULTS: Veterans with SCI&Ds had a total of 11,113 ARI visits over the 5-year period. There was a slightly decreasing trend for LRI visits over time (P < 0.01) but no significant change for other ARIs over time. There were 30 to 35 pneumonia visits and 21 to 30 acute bronchitis visits per 1,000 SCI&D veterans per year. Older veterans were more likely than younger to have P&I visits and less likely to have URI visits (P < 0.01). Veterans with paraplegia had fewer P&I visits than subjects with tetraplegia (IRR = 0.58; Cl = 0.51-0.67). CONCLUSIONS: Visit rates for ARIs are stable for veterans with SCI&Ds. Identifying risk factors associated with ARI visits is an important first step to improve prevention and treatment of ARIs and to improve the health of veterans with SCI&Ds.

Effect of nutritional counselling on hepatic, muscle and adipose tissue fat content and distribution in non-alcoholic fatty liver disease.

AIM: To assess the effectiveness of the current UK clinical practice in reducing hepatic fat (IHCL). METHODS: Whole body MRI and (1)H MRS were obtained, before and after 6 mo nutritional counselling, from liver, soleus and tibialis muscles in 10 subjects with non-alcoholic fatty liver disease (NAFLD). RESULTS: A 500 Kcal-restricted diet resulted in an average weight loss of 4% (-3.4 kg,) accompanied by significant reductions in most adipose tissue (AT) depots, including subcutaneous (-9.9%), abdominal subcutaneous (-10.2%) and intra-abdominal-AT (-11.4%). Intramyocellular lipids (IMCL) were significantly reduced in the tibialis muscle (-28.2%). Decreases in both IHCL (-39.9%) and soleus IMCL (-12.2%) content were also observed, although these were not significant. Several individuals showed dramatic decreases in IHCL, while others paradoxically showed increases in IHCL content. Changes in body composition were accompanied by improvements in certain liver function tests: serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Significant correlations were found between decreases in IHCL and reductions in both intra-abdominal and abdominal subcutaneous AT. Improvements in liver function tests were associated with reductions in intra-abdominal AT, but not with changes in IHCL. CONCLUSION: This study shows that even a very modest reduction in body weight achieved through lifestyle modification can result in changes in body fat depots and improvements in LFTs.

Role of microbubble ultrasound contrast agents in the non-invasive assessment of chronic hepatitis C-related liver disease.

Patients who are chronically infected with the hepatitis C virus often develop chronic liver disease and assessment of the severity of liver injury is required prior to considering viral eradication therapy. This article examines the various assessment methods currently available from gold standard liver biopsy to serological markers and imaging. Ultrasound is one of the most widely used imaging modalities in clinical practice and is already a first-line diagnostic tool for liver disease. Microbubble ultrasound contrast agents allow higher resolution images to be obtained and functional assessments of microvascular change to be carried out. The role of these agents in quantifying the state of hepatic injury is discussed as a viable method of determining the stage and grade of liver disease in patients with hepatitis C. Although currently confined to specialist centres, the availability of microbubble contrast-enhanced ultrasound will inevitably increase in the clinical setting.

Current and future applications of magnetic resonance imaging and spectroscopy of the brain in hepatic encephalopathy.

Hepatic encephalopathy (HE) is a common neuro-psychiatric abnormality, which complicates the course of patients with liver disease and results from hepatocellular failure and/or portosystemic shunting. The manifestations of HE are widely variable and involve a spectrum from mild subclinical disturbance to deep coma. Research interest has focused on the role of circulating gut-derived toxins, particularly ammonia, the development of brain swelling and changes in cerebral neurotransmitter systems that lead to global CNS depression and disordered function. Until recently the direct investigation of cerebral function has been difficult in man. However, new magnetic resonance imaging (MRI) techniques provide a non-invasive means of assessment of changes in brain volume (coregistered MRI) and impaired brain function (fMRI), while proton magnetic resonance spectroscopy (1H MRS) detects changes in brain biochemistry, including direct measurement of cerebral osmolytes, such as myoinositol, glutamate and glutamine which govern processes intrinsic to cellular homeostasis, including the accumulation of intracellular water. The concentrations of these intracellular osmolytes alter with hyperammonaemia. MRS-detected metabolite abnormalities correlate with the severity of neuropsychiatric impairment and since MR spectra return towards normal after treatment, the technique may be of use in objective patient monitoring and in assessing the effectiveness of various treatment regimens.

Oral health of psychiatric patients: A cross-sectional comparision study.

BACKGROUND: Mental illness is associated with physical health. Oral health affects people physically and psychologically and influences how they grow, enjoy life, look, speak, chew, taste food and socialize. Oral health may have lower priority in the context of mental illness and these diverse and changing client group experiences similar oral and dental problems. OBJECTIVE: To assess oral health problems in psychiatric patients. MATERIALS AND METHODS: This cross-sectional study included 133 patients attending the psychiatric outpatient department (OPD) as the study group and 133 patients attending the general OPD of the same hospital as the control group. Both groups were examined for oral health status. RESULTS: Mean age of the study group was 40.2 years, 66.17% were males, 66.17% were married and 83.67% belonged to middle or lower class. 39.8% of patients had mental illness for 1-5 years, 88% were self sufficient and 34.6% had healthy oral practices. These results are very much comparable with the control group. Mean decayed missed filled teeth (DMFT) score (2.10) and mean oral hygiene index-simplex (OHI-S) score (3.6) increased with age. Difference in DMFT score with age was not statistically significant (P>0.5) while it was highly significant for OHI-S score (P<0.0001). Periodontal condition worsened as age increased, suggested by community periodontal index. Only 26.7% of patients had healthy gingiva in the age group 20-50 years while it was zero for 50 years and above. This difference is statistically significant (P<0.001).

Accuracy and reliability of microbubble ultrasound measurements for the non-invasive assessment of hepatic fibrosis in chronic hepatitis C.

AIM: Contrast-enhanced ultrasound can be used to assess liver disease severity non-invasively by observing intra- and extrahepatic hemodynamic changes. Transit times are calculated to include intra- and extrahepatic components (hepatic vein transit time, HVTT) or the intrahepatic component (hepatic transit time, HTT), but these have not been compared directly. We aimed to compare diagnostic accuracy of HVTT and HTT in gauging the severity of chronic hepatitis C (CHC) and to assess inter- and intra-observer reliability. METHODS: Recorded ultrasound scans performed on 75 patients with biopsy-staged CHC, using the microbubble contrast agent Sonovue were analyzed. RESULTS: Diagnostic accuracy of HTT and HVTT for diagnosis of cirrhosis was 0.78 and 0.71 (P = 0.24). Diagnostic accuracy of HTT and HVTT for diagnosis of fibrosis stage >2 was 0.76 and 0.72 (P = 0.23). Negative predictive value for cirrhosis using this cut-off was high for both techniques (HVTT, 88%; HTT, 92%), suggesting utility for exclusion of cirrhosis. Inter-observer reliability for HTT and HVTT were 0.92 and 0.94, respectively. Intra-observer reliability for HTT and HVTT were 0.98 and 0.99. CONCLUSION: In this cohort, reliability exceeded 90% while diagnostic accuracy was in keeping with previous studies of microbubble transit time analysis. Despite higher numerical diagnostic accuracy for HTT, no significant difference was demonstrated between the techniques, suggesting that both methods can be used reliably.

Percutaneous vertebroplasty: role in treatment of vertebral compression fractures.

Osteoporosis is the most common metabolic bone disorder. Vertebral compression fractures (VCFs) are a significant cause of back pain. Pain after VCF can be attributed to incomplete healing and progressive collapse of the bone. Conservative management has been the historical treatment option for patients with painful percutaneous vertebroplasties (PVs). Although seemingly harmless, conservative treatment can be risky for elderly patients suffering from VCFs. PV can be used to treat VCFs in some patients. The exact mechanism of pain relief by vertebroplasty is not understood; the pain relief is probably because of improved vertebral body strength and stiffness and decreasing motion of the vertebral body and periosteal and interosseous nerves. But, PV is not without risks. Therefore, until further studies show that PV is superior to conservative treatment, with equivalent complications profile, PV should be reserved for patients who have failed conservative treatment.

Perihepatic lymph nodes as markers of disease response in patients with hepatitis C-related liver disease: a prospective clinical evaluation.

AIM: To assess the clinical feasibility of utilizing the presence of perihepatic lymphadenopathy, seen on ultrasound, as a marker of response to antiviral treatment in patients with hepatitis C virus (HCV)-related liver disease. METHODS: Eighty-five patients with HCV-related liver disease [51 men and 34 women; mean age 47 years (range 26-67)] underwent liver biopsy and baseline ultrasound scans. Twenty-two of these patients were followed up longitudinally with 6-monthly ultrasound scans, whereas they were receiving anti-HCV eradication therapy with interferon and ribavirin. Perihepatic lymph nodes detected in the coeliac axis and peripancreatic region were noted, with the largest node size on maximal diameter recorded. The patients were subsequently assessed in the light of long-term virological response to treatment. RESULTS: Perihepatic lymph nodes were detected in 26 of the 85 patients. Of the 22 patients followed up longitudinally, 11 responded to antiviral treatment, nine failed to respond and two did not complete a course of treatment. No significant difference was found between patients with detectable lymphadenopathy and those without according to age, sex, disease severity and genotype. There was a general reduction in size of lymph nodes in both responders and nonresponders to treatment, although this reduction was only significant in the responder group (P=0.003). CONCLUSION: The presence of perihepatic lymphadenopathy when detected in patients with viral hepatitis can potentially serve as an indicator of response to treatment. However, as only 30-40% of patients have detectable lymphadenopathy, its clinical utility is limited.

Proton magnetic resonance spectroscopy and ultrasound for hepatic fat quantification.

AIM: The increasing prevalence of fatty liver disease requires routine assessment methods. Proton magnetic resonance spectroscopy ((1)H MRS) is increasingly used for steatosis measurement, but due to cost, is unlikely to become a widely-used screening tool. Ultrasound is cheaper and more widely available, although subject to observer variability. Our aim was to determine the sensitivity and specificity of ultrasound against (1)H MRS, using MRS as a gold standard, for the detection and quantification of hepatic fat content. METHODS: Fifty adults participated (43 men, seven women) in this study. Hepatic steatosis was assessed by ultrasound and (1)H MRS. Images were graded by two independent radiologists to classify severity and distribution of liver fat. RESULTS: Ultrasound detected liver fat infiltration in 82% of cases measurable by (1)H MRS, while liver fat was detectable in 44% of cases graded absent by ultrasound. Ultrasound grading was subjective, with the radiologists in agreement in 53% of cases (kappa = 0.39, P = 0.002). Considerable overlap in intrahepatocellular lipid content was observed between different grades: absent (0.0-1.58%), mild (2.2-16.2%), moderate (4.9-26.7%) and severe (8.1-76.8%) steatosis. Ultrasound could not detect liver fat levels below 2% as measured by (1)H MRS Conclusion: Ultrasound is less sensitive than (1)H MRS in detecting very low levels of liver fat content, but is sensitive to fatty infiltration greater than 2%. There is a tendency of higher ultrasound grades to correlate with higher degrees of fatty infiltration, although some overlap exists. Our findings are still consistent with ultrasound being useful as a low cost screening tool.

Outcomes of outpatient visits for acute respiratory illness in veterans with spinal cord injuries and disorders.

OBJECTIVE: Respiratory complications are a leading cause of death in persons with spinal cord injuries and disorders (SCI&D). We examined same-day and 60-day hospitalizations and 60-day mortality after acute respiratory illness (ARI) outpatient visits. DESIGN: A longitudinal study was conducted of 8775 ARI visits in the Veterans Health Administration (VA) (October. 1997-September 2002) by persons with SCI&D. ARIs included upper respiratory infections (URI), acute bronchitis, pneumonia, and influenza (P&I). RESULTS: URIs accounted for almost half of all (49%) visits. A total of 14.9% of patients with ARIs were hospitalized the same day; 30.8% were hospitalized within 60 days. Predictors of hospitalization included diagnosis of either P&I or acute bronchitis, comorbid illness, level of injury, age, and VA SCI center visit. Overall 60-day mortality was 2.9% but was 7.9% for pneumonia. Mortality was related to diagnosis (P&I: odds ratio [OR] = 9.80, 95% confidence interval [CI]: 6.27-13.33; acute bronchitis: OR = 2.00, 95% CI: 1.08-2.93), age (65+: OR = 3.96, 95% CI: 2.23-5.70), and comorbid conditions (OR = 1.94, 95% CI: 1.43-2.46). CONCLUSIONS: P&I and acute bronchitis were associated with increased VA hospitalization and mortality rates. The case fatality rate for pneumonia is higher for SCI&D than the general population. Level of injury predicted hospitalization but not death. Efforts to improve prevention and treatment of ARIs in persons with SCI&D are needed.

Hepatic vein transit time of SonoVue: a comparative study with Levovist.

PURPOSE: To prospectively compare transit times of Levovist and SonoVue in healthy volunteers and patients with biopsy-proved hepatitis C-related liver disease. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Forty patients and 25 healthy volunteers were examined. Subjects fasted, a bolus of SonoVue (0.6 mL) was injected into a cubital fossa vein, and hepatic venous time-intensity profiles were measured with spectral Doppler tracing. This was repeated with two injections of Levovist (2 g) and another injection of SonoVue. Time-intensity curves of spectral Doppler signals of right and middle hepatic veins were analyzed. A sustained signal intensity increase of 10% above baseline levels indicated hepatic vein transit time (HVTT). Carotid artery audio intensity was measured in volunteers. Analysis of variance and t tests were used for statistical analysis. RESULTS: Twelve patients had mild hepatitis; 18, moderate or severe hepatitis; and 10, cirrhosis. Mean HVTTs in control, mild hepatitis, moderate or severe hepatitis, and cirrhosis groups were 38.3 seconds +/- 2.4 (standard error), 47.5 seconds +/- 6.5, 29.5 seconds +/- 10.8, and 17.6 seconds +/- 5.0, respectively, with Levovist (P < .001) and 29.4 seconds +/- 6.9, 27.4 seconds +/- 9.3, 22.9 seconds +/- 4.7, and 16.4 seconds +/- 4.9, respectively, with SonoVue (P < .001). HVTT decreased as severity increased at imaging with both contrast agents. There was no significant difference in HVTT between mild and moderate hepatitis groups with SonoVue; however, there were significant differences in HVTT between all patient groups with Levovist. HVTT of SonoVue was shorter than that of Levovist in all groups (P < .001) except the cirrhosis group; in this group, HVTT of the two contrast agents was similar (P = .05). No difference was observed in mean cardiopulmonary transit time for SonoVue or Levovist (9.1 seconds +/- 2.4 [standard error] and 8.4 seconds +/- 2.5, respectively, P = .18). CONCLUSION: HVTT was significantly shorter with SonoVue than with Levovist; there was no significant difference in cardiopulmonary transit time.

Variations due to analysis technique in intracellular pH measurements in simulated and in vivo 31P MR spectra of the human brain.

PURPOSE: To investigate variation in pH generated by different analysis techniques and to find the most robust method, 31P MR brain spectra were acquired in vivo. Three different methods were used to measure the chemical shift of inorganic phosphate (Pi) relative to phosphocreatine (PCr). MATERIALS AND METHODS: Eight healthy volunteers were scanned four times, and manual measurement of the chemical shift in a frequency domain spectrum using the manufacturer's software was compared with values produced by a frequency-domain analysis method (NMR1) and a prior-knowledge-based time-domain technique (MRUI). To explain the in vivo data, simulations of brain spectra, modified in ways typical of real variations in vivo, were produced and the pH was measured using manual measurement and MRUI. RESULTS: Different measurement techniques produced systematically different pH values, with manual measurement producing the lowest variability (manual measurement: pH = 6.999, CoV = 0.297; NMR1: pH = 7.042, CoV = 0.501; MRUI: pH = 7.036, CoV = 0.606). While MRUI more accurately measured the pH of unaltered simulations, it was systematically affected by altering the simulated spectra. Manual measurement was unaffected. CONCLUSION: Manual measurement produces the most consistent pH value, and there is no benefit in using more complex automated spectral fitting methods to measure the pH.

Can Doppler sonography grade the severity of hepatitis C-related liver disease?

OBJECTIVE: Many authors have claimed that Doppler sonography indexes are of value in grading and assessing diffuse liver disease. However, there is much controversy regarding the reliability and reproducibility of these techniques. We performed a prospective study to evaluate whether these methods can grade disease in a well-stratified cohort of patients with hepatitis C virus (HCV)-related liver disease. SUBJECTS AND METHODS: Sixty-five patients with biopsy-proven HCV-related liver disease were recruited, and Doppler sonography was performed by one operator. The patients were classified into one of the following three groups on the basis of the Ishak-modified histologic activity index (HAI) fibrosis (F) and necroinflammatory (NI) scores: mild hepatitis (F < or = 2 and NI < or = 3), moderate or severe hepatitis (3 < or = F < 6 or NI > or = 4), or cirrhosis (F = 6/6). We measured the following Doppler indexes: main hepatic artery peak velocity (Vmax) and resistive index, main portal vein peak velocity (Vmax), and maximal portal vein diameter and circumference that allowed calculation of the portal vein congestive index (portal vein area and portal vein velocity). The ratio of the hepatic artery velocity (Vmax) to the portal vein velocity (Vmax) was also calculated, and the phasicity (triphasic, biphasic, or monophasic) of the hepatic veins of each patient was recorded. We also measured the maximal spleen length longitudinally. RESULTS: A total of 65 patients with liver disease (mild hepatitis, n = 20; moderate or severe hepatitis, n = 25; cirrhosis, n = 20) with biopsy-proven HCV-related liver disease were studied. Optimal hepatic arterial traces were obtained in only 30 patients and portal vein circumference in 18 patients. No significant differences were observed in the Doppler indexes with increasing severity of liver disease. Five (29%) of 17 patients with mild hepatitis had an abnormal hepatic vein trace (i.e., biphasic or monophasic) compared with 11 (55%) of 20 patients with moderate or severe hepatitis and 12 (60%) of 20 patients with cirrhosis. The only index to show a significant intergroup difference was splenic length (analysis of variance, p < 0.001), but there was still overlap between the groups. CONCLUSION: Doppler-derived indexes, which have previously been recommended for the assessment of severity in chronic liver disease, are difficult to reproduce reliably and therefore have a limited clinical role in the noninvasive assessment of hepatic fibrosis or inflammation.

Changes in brain size in hepatic encephalopathy: a coregistered MRI study.

Magnetic resonance imaging (MRI) coregistration techniques can be used to track changes in brain volume. We aimed to determine whether treatment in chronic liver disease altered brain size. The study group comprised nine patients with cirrhosis (7 Child's grade B and 2 Child's grade C). Six had minimal and three had overt hepatic encephalopathy on clinical, psychometric, and electrophysiological testing. Cerebral MRI was performed in seven patients before and 6 weeks after starting lactulose. A further two patients underwent transjugular intrahepatic portosystemic stent shunting with MRI performed before and 24 h afterwards. One patient had a further scan 3 months after TIPSS. Brain size was measured using a semiautomated contour/thresholding technique. Measurable changes were found after treatment intervention, but there was no correlation with severity of encephalopathy (West Haven criteria) or liver dysfunction (Child's score). Three patients improved on lactulose, the brain size decreased with an increase in ventricular volume. Two patients deteriorated; the brain size increased with a concomitant decrease in ventricular volume. Two stable patients had small changes, one with an increase in brain size and a decrease in ventricular volume and the other showing the converse. Following TIPSS, there was an increase in brain size in both patients, evident within 24 h in one patient and at 3 months in the other. Coregistered MRI demonstrates easily detectable changes in brain size following treatment intervention. Our results support the hypothesis that low-grade brain swelling is present, even in minimal hepatic encephalopathy.

Prior knowledge for time domain quantification of in vivo brain or liver 31P MR spectra.

Prior knowledge is required when quantifying in vivo (31)P magnetic resonance spectra from the brain or liver. The prior knowledge system we have used models both the phosphomonoester and phosphodiester resonances as two peaks of equal linewidth and fixed relative chemical shift. The analysis of the data is carried out in the time domain, which allows the broad component of the spectra to be modelled. This prior knowledge method has been tested for analysis of in vivo (31)P MR spectra from the liver and brain and gives results consistent with other methods that are also used to analyse the spectra, but with reduced variability. This technique may be utilized for studies requiring serial MR spectroscopy examinations, before and after patient treatment.