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Biomedical subjects

W J Miller

Publications and source records attributed to W J Miller.

At least 73 records · Page 4Linked to original sources

Hepatic parenchymal perfusion defects detected with CTAP: imaging-pathologic correlation.

To determine whether characteristics of focal hepatic parenchymal perfusion defects detected with computed tomographic arterial portography (CTAP) correlate with underlying pathologic processes, 245 perfusion defects detected with CTAP in 60 patients who subsequently underwent definitive hepatic surgery were characterized by shape, location within the liver, and relative attenuation value and were prospectively correlated with sectioned pathologic specimens. Of 177 round perfusion defects, 102 (58%) were malignant and 75 (42%) were benign. Only one (2%) of 53 peripheral wedge-shaped defects was malignant. All 15 peripheral flat defects were benign. Defects in characteristic locations anterior to the porta hepatis (n = 15) and adjacent to the intersegmental fissure (n = 7) were uniformly benign. While 83 (56%) of 147 soft-tissue attenuation defects were malignant, only four (6%) of 68 intermediate-attenuation defects were malignant. Although these characteristics of parenchymal perfusion defects aid in differentiation of benign from malignant processes, all other types of perfusion defects are nonspecific and may require biopsy.

Adenoma, Bile Duct↗

Changes in extrahepatic bile duct caliber in liver transplant recipients without evidence of biliary obstruction.

To better understand changes in the size of the extrahepatic bile duct after liver transplantation, we retrospectively studied the luminal diameter of the extrahepatic bile duct on serial cholangiograms in 40 liver transplant recipients with choledochocholedochostomy biliary anastomoses and without biliary complications. Forty operative and 105 postoperative cholangiograms were reviewed. The average interval between operative and last postoperative cholangiogram was 5 weeks (range, 1-17 weeks). The mean diameter of the donor common hepatic duct increased from 5.5 +/- 2.1 mm to 6.3 +/- 2.4 mm (p = .015). The mean diameter of the native common bile duct increased from 5.1 +/- 1.4 mm to 6.8 +/- 2.4 mm (p less than .001). The diameter of the donor common hepatic duct increased by 3 mm or more in six patients (15%); the diameter of the native common bile duct increased by 3 mm or more in nine (23%). Increased diameter of the native common bile duct was associated with T-tube migration into the duct in four cases. The size of the extrahepatic bile duct on cholangiograms is stable or increases slightly in most liver transplant recipients. Mild increases unassociated with a specific cause of obstruction or hepatic dysfunction do not portend biliary obstruction and are clinically benign.

Bile Ducts↗

Epithelioid hemangioendothelioma of the liver: imaging findings with pathologic correlation.

Hepatic epithelioid hemangioendothelioma is a rare malignant neoplasm that has nonspecific clinical signs and symptoms and can be difficult to diagnose on the basis of biopsy results. Radiologists may suggest the diagnosis of this slowly progressive neoplasm by recognizing its characteristic radiologic features. We correlated images from CT (13), sonography (nine), and MR (six) with pathologic findings in resected whole livers (eight) and biopsy specimens (five) from 13 patients 25-58 years old. Gross pathologic examination showed a repetitive pattern of multiple solid tumor nodules, in a predominantly peripheral distribution, with coalescence as individual nodules exceeded 4 cm. Tumor nodules had a hyperemic rim. Lesions adjacent to the capsule often produced capsular retraction. These findings correlated well with imaging findings. On CT, the lesions were of low attenuation, peripherally based, and with capsular retraction or flattening in nine (69%) of 13 patients. Unenhanced CT scans showed superior conspicuity over contrast-enhanced CT scans (9/13, 69%) and showed the extent of lesions more accurately in all cases (13/13, 100%). In nine patients, lesions had a peripheral enhancement pattern of alternating attenuation values correlating with the hyperemic rim at pathologic evaluation. On sonograms, the tumors were solid and predominantly hypoechoic. On MR, tumor signal was low on T1-weighted and high on T2-weighted images, with a low-signal halo present around many of the lesions. CT, sonographic, or MR findings of coalescent peripheral hepatic masses with capsular retraction are highly suggestive of hepatic epithelioid hemangioendothelioma.

Adult↗

Detection of malignant tumors in end-stage cirrhotic livers: efficacy of sonography as a screening technique.

OBJECTIVE: Patients with hepatic cirrhosis are at an increased risk of developing primary malignant tumors of the liver. If these tumors are discovered early, current therapies may be curative. We conducted a prospective study to assess the accuracy of sonographic screening for the detection of malignant tumors in cirrhotic livers as determined by correlation with resected whole livers. SUBJECTS AND METHODS: A total of 200 prospectively interpreted preoperative sonograms from 200 patients with cirrhosis who underwent hepatic transplantation were correlated with specimens of freshly resected whole livers. The results were analyzed to determine the sensitivity and specificity of sonography in identifying patients with malignant tumors and detecting individual tumors in each patient. RESULTS: Pathologic examination showed 80 malignant lesions in 34 patients (28 with hepatocellular carcinoma, three with cholangiocarcinoma, two with metastases, and one with non-Hodgkin's lymphoma) and three hemangiomas in two patients. Sonography correctly showed malignant tumors in 17 of the 34 patients, for a sensitivity of 50%. Sonograms were false-positive for malignant tumors in three patients, two of whom had a total of three hemangiomas. Sonography correctly showed 36 of the 80 malignant lesions, for a lesion sensitivity of 45% and specificity of 98%. Of the 44 missed lesions, 24 were 1 cm or less, 12 were between 1 and 3 cm, and eight were more than 3 cm in diameter. CONCLUSION: Our results show that sonography is highly insensitive in the detection of malignant lesions in end-stage cirrhotic livers and thus is not a reliable screening technique. However, because of sonography's very high specificity, any sonographically identified lesion in a cirrhotic liver should be considered malignant until proved otherwise.

Carcinoma, Hepatocellular↗

Senior medical students as simulated patients in an objective structured clinical examination: motivation and benefits.

Third and fourth year medical students were recruited to participate as simulated patients and examiners in an Objective Structured Clinical Examination (OSCE) administered for second year medical students. Students reported they were motivated to participate, not only by the honorarium, but because they believed the OSCE would be fun and interesting and because they were interested in medical education and in improving clinical evaluation. The third and fourth year medical students benefitted academically and financially from participation. Faculty benefitted by having a readily available source of enthusiastic and knowledgeable simulated patients.

Education, Medical, Undergraduate↗

Relapse of acute leukemia presenting as acute cholecystitis following bone marrow transplantation.

Though included in the differential diagnosis of jaundice and abdominal pain, acute acalculous cholecystitis is an uncommon hepatobiliary complication of bone marrow transplantation. Leukemic infiltration of the gallbladder presenting as acute cholecystitis is rare. We describe two cases of acute cholecystitis following marrow transplantation that represented an unexpected relapse with leukemic infiltration of the gallbladder wall.

Acute Disease↗

Blood types in cattle of Iberian ancestry and in Holsteins at various altitudes.

Gene frequencies of RBC antigens were determined in Holsteins and Colombian (criollas) cattle living at 3,000 m, and in cattle descended from fighting bulls (Vacas de lidia) living at 2,500 m. These frequencies were compared with those of Holsteins, cattle native to Florida (scrub cattle), longhorns, and native cattle from Brazil (caracu cattle) living at sea level. The criollas, Vacas de lidia, scrub cows, longhorns, and caracu are descendants of original Iberian stock introduced to the Americas. We found that despite common ancestry (scrub cattle, long-horns, criollas, and caracu), genetic differences may have been derived through years of demographic isolation. The most remarkable blood-group differences were found in the high prevalence of the B system phenogroup (heritable group of antigenic factors) BQA'G'34 in the Vacas de lidia, and of the S system phenogroup U1H' in these cattle and in caracu. Furthermore, the gene frequencies differed in the Holsteins maintained at moderately high altitude (descended from Holsteins kept at sea level), and may have been reflective of the need to adapt to moderately high altitude and chronic hypoxemic conditions. Blood group polymorphism was found in all groups of cattle, although it was reduced in the Vacas de lidia, possibly because their breeding has been carefully controlled and they appear to be highly inbred.

Altitude↗

Acute graft-versus-host disease following unrelated donor marrow transplantation: failure of conventional therapy.

The response to therapy of acute graft-versus-host disease (GVHD) is uncertain in recipients of unrelated donor (URD) bone marrow transplant (BMT). We analysed the outcome of treatment in 42 patients with moderate/severe acute GVHD. Initial therapy consisted of prednisone 60 mg/m2 orally daily for 7 days (n = 42), followed by anti-thymocyte globulin (ATG) 15 mg/kg i.v. twice daily for 8-10 doses after prednisone failure (n = 22). A clinical Stage Score for acute GVHD was determined initially and after 7, 14, 21, and 28 days of prednisone or ATG. Treatment failure represented worsening score after 7 days, involvement of a new organ or failure to improve after 14-28 days. Prednisone treatment led to 10 of 41 (24%) patients improving, while secondary therapy with ATG led to four of 21 (19%) improving. Of 42 patients treated, only nine (21%) achieved a complete and continuing response of acute GVHD by day +100. Neither age, diagnosis, recipient/donor gender status, histocompatibility nor GVHD prophylaxis regimen was associated with more frequent responses. Response to GVHD therapy was significantly correlated with survival at 100 days and 1 year post-BMT. We conclude that prednisone and ATG used for treatment of acute GVHD following URD BMT are associated with a high failure rate and that more aggressive therapy is warranted in these patients.

Acute Disease↗

Detection of antibody to the PreS2 sequence of the hepatitis B virus envelope protein using an immuno-ligand assay with a silicon sensor detection system.

Sensitive immunoassays are essential for establishing the efficacy of recombinant vaccines to hepatitis B virus (HBV). These experimental vaccines include the PreS2 and S domains of the HBV envelope protein. To facilitate measurement of antibody against HBV PreS2, we employed the immuno-ligand assay with silicon sensor-based detection. Labeling of immune reagents with the haptens biotin and fluorescein allows adaptation to the immunofiltration light addressable potentiometric sensor (LAPS) system. A biotinylated monoclonal anti-PreS2 antibody and anti-PreS2 in clinical serum samples competitively bind in liquid phase to a fluorescein labeled PreS2 + S antigen. Streptavidin mediates the immobilization on biotinylated nitrocellulose membranes. Fluorescein mediates binding of an anti-fluorescein urease conjugate to the immune complex. Urease serves as the signal-generating component which subsequently is measured in the LAPS reader. In comparison to a competitive RIA, the immuno-ligand assay demonstrated a four-fold improved sensitivity using a smaller sample volume. The higher sensitivity resulted in earlier detection of seroconversion during a clinical vaccine study.

Antibodies, Monoclonal↗

Antibody assays suitable for assessing immune responses to live varicella vaccine.

An enzyme-linked immunosorbent assay for antibodies to varicella-zoster virus (VZV), using purified viral glycoproteins as antigen (gpELISA), was compared with other assays for measuring vaccine-induced antibody responses. The gpELISA was more sensitive than conventional assays, proved highly specific for VZV and agreed well with an assay for neutralizing antibody activity. It was successfully applied to large-scale testing of live varicella vaccine in humans.

Antibodies, Viral↗

Comparing students' feedback about clinical instruction with their performances.

Validation of students' feedback as a measure of teaching effectiveness has been problematic for courses teaching clinical skills. This is true in part because establishing a valid and reliable method of assessing students' mastery of clinical skills has been a stumbling block. Reported here is the correlation of students' performances on an objective structured clinical examination (OSCE) with previously and independently collected feedback from students. In 1987-88, 190 second-year medical students at the University of Minnesota Medical School--Minneapolis spent one fourth of a second-year clinical skills course on neurology randomly assigned to one of four teaching sites--hospitals A, B, C, and D. Following their rotations, 180 of the students completed usable feedback forms. The students were consistently and significantly more positive about the teaching at hospital A. At the end of the year, all 190 students were tested using an OSCE having 20 stations, four of which presented neurologic problems. The students who had the neurology course at hospital A performed better on all four neurology problems, and differences were statistically significant for two of the problems. Feedback in this case accurately reflected a more effective teaching program.

Education, Medical, Undergraduate↗

bcr/abl mRNA detection following bone marrow transplantation for chronic myelogenous leukemia.

We have utilized the polymerase chain reaction (PCR) to sensitively detect persistence of the chronic myelogenous leukemia (CML) malignant clone and to study bcr/abl mRNA splicing patterns following bone marrow transplantation. Thirteen of sixteen patients displayed persistent malignant cells during post-BMT clinical remission. In two patients bcr/abl mRNA was detected 4 and 9 months prior to clinical relapse. In eleven of fourteen patients in continued clinical remission malignant cells were detected post-BMT. Ten of these eleven patients were also cytogenetically normal. Seven patients have lost all evidence of bcr/abl transcript, but only at 1-2 years posttransplant, while four have shown persistence of the bcr/abl transcript from 28 days to 3 years post-BMT and one has converted from an initially negative result at 1 year post-BMT to detectable levels of chimeric mRNA at 2 years. Thus, 8/9 patients tested at or before 6 months, 7/12 at 1 year, and 3/10 at 2 years showed persistent detectable CML cells. Intriguingly, mRNA splicing patterns changed in 5 patients following BMT, with complete loss of mRNA containing bcr exon 3 (n = 2) or new appearance of mRNA not containing bcr exon 3 (n = 2). A single patient transiently lost evidence of bcr exon 3 expression while persistently expressing the bcr exon 2/abl exon 2 splice. Our data suggest that the majority of patients harbor small numbers of malignant cells following transplantation, and that such persistence may not inevitably predict clinical relapse. Complete elimination of the malignant CML clone post-BMT may rely on immunological mechanisms (e.g., graft-vs-leukemia).

Base Sequence↗

Obstructive dilatation of extrahepatic recipient and donor bile ducts complicating orthotopic liver transplantation: imaging and laboratory findings.

Biliary obstruction in liver transplants is most commonly due to stricture at the biliary anastomosis. The native common bile duct typically is normal. We retrospectively studied 28 patients with choledochocholedochostomy anastomoses who had marked native and donor extrahepatic bile duct dilatation associated with clinical evidence of biliary obstruction. Operative cholangiograms were compared with postoperative cholangiograms obtained a mean of 50 weeks (range, 2-246 weeks) later. Mean caliber of the native common bile duct increased from 7.5 +/- 2.0 mm on operative cholangiograms to 14.8 +/- 3.9 mm on postoperative cholangiograms (p less than .001). Mean caliber of the donor common hepatic duct increased from 5.9 +/- 1.3 mm on operative cholangiograms to 12.8 +/- 3.8 mm on postoperative cholangiograms (p less than .001). Dilatation of the cystic duct remnant was seen in 15 patients. All patients had surgical revision to choledochojejunostomy with improved results of liver function studies in most cases. Diffuse dilatation of native and donor extrahepatic bile ducts may develop in liver transplant recipients. Typical features include native and donor extrahepatic ducts greater than 12 mm in diameter and a dilated cystic duct remnant on postoperative cholangiography in a patient with otherwise unexplained hepatic dysfunction.

Adult↗

Diagnosis and staging of hepatocellular carcinoma: comparison of CT and sonography in 36 liver transplantation patients.

Radiologic studies are important in the detection of hepatocellular carcinoma and the selection of patients for partial liver resection, liver transplantation, or palliation. We retrospectively studied 36 patients with hepatocellular carcinoma who were examined with both CT and sonography before undergoing hepatic transplantation. Pathologic findings of the entire resected liver were correlated with results of imaging studies before transplantation. Parenchymal lesions were shown by sonography in 29 cases (81%) and by CT in 34 cases (94%). Although CT was more sensitive than sonography was, both CT and sonography frequently failed to depict reliably the size of tumor or the exact number of tumor nodules as determined pathologically. Pathologic findings showed vascular invasion in 19 cases (53%), whereas CT showed invasion in 11 cases (31%) and sonography showed it in only six (17%). Nodal metastasis to the porta hepatis was found in four patients; CT correctly showed two cases (three false-positive) and sonography correctly showed one case. Intrahepatic ductal dilatation was seen in eight patients on CT but was not identified on sonography. We conclude that CT is more accurate for identifying and staging hepatocellular carcinoma, but both CT and sonography frequently fail to depict the extent (size and number of lesions) of disease, especially when underlying cirrhosis is present.

Adolescent↗

Zinc absorption, metabolism, and endogenous excretion in zinc-deficient and normal calves over an extended time.

Zinc metabolism was studied in Zn-deficient and control Holstein calves over a 2-mo period following a single oral or i.v. 65Zn dose. In both orally and i.v. dosed animals, all gastrointestinal tissue sections from Zn-deficient animals contained more 65Zn than comparable tissues of controls. Contents of proximal small intestinal sections of Zn-deficient calves contained more 65Zn 8 to 10 wk after dosing than did those from controls; however, the reverse occurred in the distal small intestine, cecum, and large intestine. With both dosing methods, Zn-deficient calves retained more 65Zn throughout the study. Daily 65Zn excretion rate as a percentage of that retained declined for 6 wk after dosing, indicating a constantly increasing biological half-life. For deficient calves, the biological half-life was about 500 d in the later weeks of the experiments. In orally dosed, Zn-deficient animals, specific activity of fecal 65Zn exceeded that of serum Zn throughout the study. This shows a shortcoming in the basic assumption of measuring endogenous Zn loss from fecal and serum specific activities and total fecal stable Zn. Thus, endogenously excreted Zn is not representative of that remaining.

Animals↗

Special report on taxation. Prepare for impending legislation that could threaten your tax-exempt status!

With impending federal action, and the likelihood of "copycat" legislation at the state and local levels if a federal statue is adopted, nonprofit hospitals need to ensure that they will be in compliance if a mandatory charity care bill were to become law. Such facilities should take the initiative now, by clearly articulating their charity care policies and by describing their other undercompensated or uncompensated activities that are maintained in order to benefit their communities. They should also ensure that all of their activities that could be counted as charity care or community benefit are fully documented and quantified. Financial consultants and counsel may be helpful in this process. Exempt facilities also should, of course, closely monitor the progress of the bills discussed above. Most importantly, they should continue to test their charity care and community benefit statistics on a regular basis to determine if their facilities meet the thresholds specified in the bills as they proceed through Congress.

Charities↗

Prevention of cytomegalovirus infection following bone marrow transplantation: a randomized trial of blood product screening.

From 1983 to 1987, cytomegalovirus seronegative allogeneic bone marrow recipients were randomized to receive screened cytomegalovirus (CMV) seronegative or unscreened blood products and 125 patients were available for analysis. CMV infection occurred in 18% of patients in the screened versus 38% in the unscreened blood product group. However, only two of 64 patients in the screened group and seven of 61 in the unscreened group developed culture or biopsy-proven CMV infections. Bone marrow donor CMV seropositivity was associated with an increased risk of developing CMV infection (21% with seronegative and 46% with seropositive donor), and CMV infection was not prevented by blood product screening if the bone marrow donor was sero = positive (62% for screened, 42% for unscreened group, p = 0.80). One year survival censored for relapse was 52% in the screened group versus 68% in the unscreened group (p = 0.08). Gram negative bacteremia complicated bone marrow transplantation (BMT) in 35% of patients receiving screened and 15% of those receiving unscreened blood products (p = 0.02). Relapse did not differ in the screened and unscreened groups. By multivariate analysis, high risk disease (p = 0.0002), CMV infection (p = 0.004), screened blood products group (p = 0.011), recipient age greater than 17 (p = 0.027), chronic graft-versus-host disease (p = 0.014) and gram negative bacteremia (p = 0.004) independently had a negative influence on survival. We conclude that blood product screening was effective in preventing CMV infections following BMT if both the recipient and bone marrow donor were CMV seronegative.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗