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Biomedical subjects

S Sofia

Publications and source records attributed to S Sofia.

12 recordsLinked to original sources

Functionalized silk-based biomaterials for bone formation.

Silks are being reassessed as biomaterial scaffolds due to their unique mechanical properties, opportunities for genetic tailoring of structure and thus function, and recent studies clarifying biocompatibility. We report on the covalent decoration of silk films with integrin recognition sequences (RGD) as well as parathyroid hormone (PTH, 1-34 amino acids) and a modified PTH 1-34 (mPTH) involved in the induction of bone formation. Osteoblast-like cell (Saos-2) responses to the decorated silk films indicate that the proteins serve as suitable bone-inducing matrices. Osteoblast-like cell adhesion was significantly increased on RGD and PTH compared to plastic, mPTH, and the control peptide RAD. At 2 weeks of culture, message levels of alkaline phosphatase were similar on all substrates, but by 4 weeks, alkaline phosphatase mRNA was greatest on RGD. At 2 weeks of culture, alpha 1(I) procollagen mRNA was elevated on silk, RGD, RAD, and PTH, and hardly detectable on mPTH and plastic. However, by 4 weeks RGD demonstrated the highest level compared to the other substrates. Osteocalcin message levels detected by RT-PCR were greatest on RGD at both time points. Calcification was also significantly elevated on RGD compared to the other substrates with an increase in number and size of the mineralized nodules in culture. Thus, RGD covalently decorated silk appears to stimulate osteoblast-based mineralization in vitro.

Animals↗

Influence of esophageal varices and spontaneous portal-systemic shunts on postprandial splanchnic hemodynamics.

OBJECTIVE: The aim of the study was to assess postprandial splanchnic hemodynamic changes in cirrhosis in relation to variceal status. METHODS: In 9 healthy controls and 56 patients with liver cirrhosis, stratified according to variceal status and presence of spontaneous portal-systemic shunts, the portal vein diameter and flow velocity, the congestion index of the portal vein, and the resistive index of the superior mesenteric artery (SMA-RI) were studied by Doppler ultrasound before and 30, 60, and 120 min after the intake of a standard meal. Comparison of postprandial parameters with basal ones was done within each group by paired t test and among groups by ANOVA and Duncan test. RESULTS: Healthy controls and cirrhotic patients without varices showed similar significant splanchnic hemodynamic changes, namely a reduction of SMA-RI (-13% at 30 min) and a consequent increase in portal vein diameter (respectively, +32% and +17% in the two groups) and velocity (+66% and +51%). A significant reduction of SMA-RI was also found in patients with varices, irrespective of the variceal size (range, -7 to -11%), but the expected portal vein dilation and velocity increase were progressively blunted with the increase of variceal size (range, 0-5% for diameter and 5-19% for velocity). Patients with spontaneous portal-systemic shunts showed a response similar to that of patients with large varices. Significant modification of the congestion index of the portal vein did not occur in any group. CONCLUSIONS: Our results show that the hemodynamic response to meal in patients with liver cirrhosis is influenced by the presence and size of esophageal varices and the presence of spontaneous portal-systemic shunts.

Blood Flow Velocity↗

Surveillance programme of cirrhotic patients for early diagnosis and treatment of hepatocellular carcinoma: a cost effectiveness analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of death in cirrhotic patients. This neoplasm is associated with liver cirrhosis (LC) in more than 90% of cases. Early diagnosis and treatment of HCC are expected to improve survival of patients. AIMS: To assess the cost effectiveness of a surveillance programme of patients with LC for the early diagnosis and treatment of HCC. PATIENTS: A cohort of 313 Italian patients with LC were enrolled in the surveillance programme between March 1989 and November 1991. In the same period, 104 consecutive patients with incidentally detected HCC were referred to our centre and served as a control group. METHODS: Surveillance was based on ultrasonography (US) and alpha fetoprotein (AFP) determinations repeated at six month intervals. Risk factors for HCC were assessed by multivariate analysis (Cox model). Outcome measures analysed were: (1) number and size of tumours; (2) eligibility for treatment; and (3) survival of patients. Economic issues were: (1) overall cost of surveillance programme; (2) cost per treatable HCC; and (3) cost per year of life saved (if any). Costs were assessed according to charges for procedures at our university hospital. RESULTS: Surveillance lasted a mean of 56 (31) months (range 6-100). During the follow up, 61 patients (19.5%) developed HCC (unifocal at US in 49 cases), with an incidence of 4.1% per year of follow up. AFP, Child-Pugh classes B and C, and male sex were detected as independent risk factors for developing HCC. Only 42 (68.9%) of 61 liver tumours were treated by surgical resection, orthotopic liver transplantation, or local therapy. The cumulative survival rate of the 61 patients with liver tumours detected in the surveillance programme was significantly longer than that of controls (p=0.02) and multivariate analysis showed an association between surveillance and survival. The overall cost of the surveillance programme was US$753 226, the cost per treatable HCC was US$17 934, and the cost for year of life saved was US$112 993. CONCLUSION: Our surveillance policy of patients with LC requires a large number of resources and offers little benefit in terms of patient survival. The decision whether to adopt a surveillance policy towards HCC should rely on the prevalence of the disease in the population and on the resources of a particular country.

Adult↗

High prevalence of Helicobacter pylori in liver cirrhosis: relationship with clinical and endoscopic features and the risk of peptic ulcer.

In 153 consecutive patients with cirrhosis we assessed: (1) the prevalence of IgG to Helicobacter pylori and compared it with that found in 1010 blood donors resident in the same area; and (2) the relationships of IgG to Helicobacter pylori with clinical and endoscopic features and with the risk of peptic ulcer. The IgG to Helicobacter pylori prevalence of cirrhotics was significantly higher than in blood donors (76.5% vs 41.8%; P < 0.0005) and was not associated with sex, cirrhosis etiology, Child class, gammaglobulins and hypertensive gastropathy. In both groups, the prevalence of IgG to Helicobacter pylori was significantly higher in subjects over 40. Among patients with cirrhosis a significantly higher prevalence of Helicobacter pylori was found in patients with previous hospital admission (P = 0.02) and/or upper gastrointestinal endoscopy (P = 0.01) and patients with peptic ulcer (P = 0.0004). Multivariate analysis identified increasing age and male sex as risk factors for a positive Helicobacter pylori serology and no independent risk factors for peptic ulcer. The high prevalence of Helicobacter pylori-positive serology found in the present series is related to age and sex and might also be explained by previous hospital admissions and/or upper gastrointestinal endoscopy. Our results do not confirm the role of Helicobacter pylori as risk factor for peptic ulcer in patients with liver cirrhosis.

Adult↗

Circadian occurrence of variceal bleeding in patients with liver cirrhosis.

Several clinical events have a rhythmicity over the 24 h period. We assessed the presence of periodic rhythm in the occurrence of haematemesis in patients with liver cirrhosis under different daylight regimens, namely during standard time and during daylight savings. Over a 48 month period there were 212 consecutive admissions of 118 cirrhotics with variceal bleeding. Complete data were available for 181 episodes of bleeding: 121 (66.9%) started with haematemesis and 60 (33.1%) started with melaena. One hundred and two (56%) episodes occurred during daylight savings and 79 (44%) occurred during standard time. The cosinor test showed a 24 h biphasic peak for the occurrence of haematemesis (09.45 and 21.45 h). Moreover, a biphasic diurnal asymmetric frequency was also found by multiple component rhythmometry. The time peaks of onset of variceal haemorrhage did not change significantly during standard time and daylight savings. Patients with more than one haematemesis episode significantly bled over the same time interval. The present study confirms that over the 24 h period variceal bleeding in cirrhotic patients occurs with a predictable rhythmicity that does not seem to be under the control of the light-dark cycle. The finding of a chronorisk for variceal haemorrhage addresses specific questions for pathophysiological studies as well as for new treatment strategies.

Aged↗

Sonographic assessment of the distal end of the thoracic duct in healthy volunteers and in patients with portal hypertension.

OBJECTIVE: Our study assessed the feasibility of detecting and measuring by sonography the diameter of the thoracic duct in healthy subjects and in patients with cirrhosis and portal hypertension. We also evaluated the relationship of thoracic duct size with age and with clinical, endoscopic, and sonographic signs of portal hypertension. SUBJECTS AND METHODS: The left supraclavicular area of 24 patients with cirrhosis and 23 healthy subjects was examined with high-frequency probes using transverse and oblique scans to visualize the distal end of the thoracic duct. All patients with cirrhosis, diagnosed by liver biopsy or clinical and biochemical data, had endoscopic or sonographic signs of portal hypertension. The severity of the liver disease was determined by Child-Pugh's criteria; the diameter of portal vessels and the size of esophageal varices were also considered. RESULTS: The thoracic duct was visualized in 19 of 24 patients with cirrhosis and in 18 of 23 control subjects (percent of visualization was 79% and 78%, respectively). The diameter of the duct was larger in patients with cirrhosis than in healthy subjects (3.1 +/- 1.2 mm versus 1.9 +/- 0.5 mm; p < .0001), but no relationship was found among clinical, endoscopic, and sonographic signs of portal hypertension. A direct relationship between age and the size of the thoracic duct was found only among healthy subjects. CONCLUSION: This is the first report of the sonographic visualization of the distal end of the thoracic duct. Its diameter is small in healthy young subjects, whereas in patients with cirrhosis its increased diameter seems to be associated only with the presence of portal hypertension and not with its severity.

Humans↗

Timing of the first variceal hemorrhage in cirrhotic patients: prospective evaluation of Doppler flowmetry, endoscopy and clinical parameters.

We followed 87 cirrhotic patients with esophageal varices and without previous hemorrhage for a mean period of 24 mo to prospectively evaluate the occurrence of variceal bleeding within (early) or after (late) 6 mo from entry and the contribution of portal Doppler ultrasound parameters to the prediction of early and late hemorrhage. Clinical, biochemical, endoscopic and portal Doppler ultrasound parameters were recorded at entry. Variceal bleeding occurred in 22 patients (25.3%). Nine (40.9%) bled within the first 6 mo. Cox regression analysis identified variceal size, cherry-red spots, serum bilirubin and congestion index of the portal vein (the ratio of portal vein [cross-sectional area] and portal blood flow velocity) as the only independent predictors of first variceal hemorrhage. Discriminant analysis was used to find the prognostic index cut off points to identify patients who bled within 6 mo (prognostic group 1) or after 6 mo (prognostic group 2) or remained free of bleeding (prognostic group 3). The cumulative proportion of patients correctly classified was 73% in prognostic group 1, 47% in prognostic group 2 and more than 80% in prognostic group 3. The addition of Doppler ultrasound flowmetry to clinical, biochemical and endoscopic parameter only improved the classification of patients with early bleeding.

Adult↗

The relationship of endoscopy, portal Doppler ultrasound flowmetry, and clinical and biochemical tests in cirrhosis.

The relationship of the endoscopic aspect of esophageal varices, portal quantitative Doppler ultrasound parameters and clinical and biochemical findings was assessed in 149 patients with cirrhosis stratified according to the presence of esophageal varices (n = 115) and the absence of previous bleeding (n = 96). In this series of patients the presence of esophageal varices and red signs proved to be significantly correlated with the severity of cirrhosis. However, in the group of patients with varices, no correlation was found between variceal size and the degree of liver failure. Portal blood flow velocity was significantly different in the endoscopic subgroups, but not in the clinical and biochemical subgroups. Furthermore, portal blood flow velocity was found to correlate only with the presence and size of esophageal varices. The Congestion Index of the portal vein (derived from the ratio between the cross-sectional area of the portal vein and the mean velocity of portal flow) was significantly different in most clinical, biochemical and endoscopic subgroups and was correlated with liver function, presence and size of varices, and presence and degree of red signs. We conclude that the Congestion Index of the portal vein, the clinical status and the endoscopic aspect of varices are not independent features in patients with cirrhosis. As for liver function and endoscopic findings, portal Doppler ultrasound parameters, in particular the Congestion Index, may contribute to a better clinical assessment in patients with cirrhosis.

Endoscopy, Digestive System↗

Quantitative analysis of intrahepatic bile duct component in normal adult human liver and in primary biliary cirrhosis.

The volume density of bile ducts in adult normal liver has been analyzed in order to provide stereometric parameters to which refer on performing quantitative evaluations of bile duct loss in acquired liver diseases. Five livers were studied by applying a semi-automatic image analysis system (ASM 68K Leitz) to histological sections. No significant differences (P > 0.10) were found for all measures and the following values were derived from the pooled data: (1) mean % volume of bile ducts in liver = 0.318 +/- 0.171; (2) mean % volume of portal tracts in liver = 4.351 +/- 2.860; (3) mean % volume of bile ducts in portal tracts = 6.567 +/- 3.813. The parallelism of bile duct to arterial components of portal tracts was also investigated and expressed as the ratio of their respective volume fractions (mean ratio = 1.72). The validity of the obtained parameters was tested by comparing them with values determined in five cases of primary biliary cirrhosis (PBC). All PBC cases showed a marked decrease in both bile duct % volume in liver (ranging between 0.028 and 0.057) and bile duct % volume in portal tracts (ranging between 0.673 and 0.914), as well as inversion of the bile duct to artery volume ratio in portal tracts (ranging between 0.246 and 0.437).

Adult↗

Sonographic findings in abdominal hereditary angioedema.

Patients with hereditary angioedema (HAE) may suffer from abdominal pain severe enough to prompt unnecessary surgical intervention. The diagnostic approach to abdominal pain during HAE attacks is not established. We describe abdominal sonographic findings during severe colic in 2 patients with known HAE. Sonography demonstrated marked mucosal thickening and edema of the bowel wall with a variable amount of free peritoneal fluid. These findings are not specific but are consistent with the hypothesized mechanism of attack and resolve after therapy. Abdominal sonography is useful for evaluating acute abdominal pain in patients with known HAE to prevent unnecessary surgery. Conversely, if the described sonographic findings appear in a case of abdominal colic of unknown origin, HAE should be included in the differential diagnosis.

Abdominal Pain↗

Sonographic diagnosis of adult intussusception.

We describe three cases of adult intussusception in which ultrasonography provided the correct preoperative diagnosis. Patients underwent ultrasonography to investigate nonspecific acute abdominal pain; intussusception was not suspected. In all cases, the sonographic pattern was typical of intussusception and ultrasonography was the only diagnostic study. Bowel ischemia was not found at surgery in any patient.

Abdomen, Acute↗