Histology Course Research Articles

Treatment of Patients with Recurrent Hepatitis C after Liver Transplantation with Peginterferon Alfa-2B Plus Ribavirin

Recurrent hepatitis C virus (HCV) after liver transplantation (OLT) is a major cause of graft loss in HCV-positive patients. In this study, we evaluated the efficacy and safety of pegylated interferon alfa-2b (peginterferon) and ribavirin treatment for recurrent HCV after OLT and analyzed the influence of antiviral treatment on the histological course of recurrent hepatitis. Twenty-five patients with recurrent HCV (genotype 1 n=20 and 2-4 n=5) received peginterferon (1 mg/kg/weekly) and ribavirin (600 mg) for 48 weeks. Viral load prior to treatment was below 1,000,000 (IU/ml) in 11 of 25 patients. Sustained antiviral response was defined as undetectable HCV-RNA in serum 6 months after stopping of therapy. All patients underwent liver biopsy prior to treatment and after 72 weeks. Seventeen of 25 patients became HCV-RNA-negative after treatment (68%). Sustained virologic response (SVR) was achieved in 9/25 (36%) patients. Liver specimen showed increase of fibrosis from 1.7 to 2.0 within 72 weeks. Side effects like neutropenia (60%) and anemia (36%) were treated with G-CSF, erythropoietin, and dose reduction of peginterferon and ribavirin. The use of peginterferon is safe and effective in patients with recurrent HCV. Treatment of side effects, especially neutropenia or anemia, helped to maintain antiviral therapy. Despite a viral response of 68% during treatment, the patients showed further progress of recurrent hepatitis in liver specimen.

The use of Blackboard in the instruction of dental histology

In recent years, the use of web-based education as an instructional method has increased at universities. Web-based technology is considered a useful tool for teaching outside the classroom and offers a range of implementation options. For many instructors web-based technology serves as the mechanism for course delivery, while in other instances online activities may enhance traditional classroom instruction. Over the years our dental histology course has utilized light microscopy, power point presentations, and digital images as methods of instruction. This year we set up our freshman dental histology course on Blackboard. This is an integrated web-based support system which enabled students to access course material and to assess their own progress through online quizzes. In the present study, we sought to examine the effectiveness of Blackboard as a supplement to traditional methods and to receive feedback on the strengths/weakness of the course using the Blackboard program. The assessment was made over a two year period. In the first year, the course was taught to 67 dental students over three lecture hours and three lab hours per week using traditional methods of instruction. In the second year, students with equivalent GPA and DAT scores were instructed using web-based materials as a supplement to traditional methods. Both groups of students were evaluated using multiple choice lecture exams and light-microscopy based lab exams. There was no difference on student performance between students using traditional methods and students using Blackboard. We discovered the students liked the accessibility of course material, the confidentiality of obtaining grades and the availability of online practice quizzes.

Strategies for Controlled Delivery of Proctored Online Exams in Anatomical Sciences

The Department of Cell Biology and Anatomy (CBA) hosts the anatomy and histology courses for the medical and dental first year students at the Medical University of South Carolina (MUSC). Over the ...

Teaching histology without microscopes: The advantages of digital technology

Human Microscopic Anatomy is taught to first year medical students during the Fall semester at GWUMC. Traditionally microscope-based, in 2004 the course “went digital” after the construction of a state-of-the-art classroom that features 90 computer workstations with high resolution flat screen monitors, as well as a digital projector system. Representative samples of each of the 100 slides in the students’ slide boxes were digitally scanned by Bacus Labs Inc. (Chicago, IL). Bacus software allows students to bring up the scanned specimens on the monitor, select any area, and magnify that area up to 40X. This technology closely mimics the learning experience of conventional microscopes, often with better images. After two years, we have noted several important advantages. Because each student looks at the same specimen for a given slide, we created a new laboratory manual with full-color thumbnail versions of each specimen, with major landmarks labeled for easy orientation; pre-lab orientation tours are also facilitated. Faculty/student interaction and teaching efficiency are fostered, as several students can view the monitor while the instructor navigates through the slide and answers questions, offering impromptu mini-lectures or testing student learning. We have improved our slide collection by adding specimens from the large library of scanned slides available through Bacus. Students appreciate that they do not have to use microscopes, but are not missing any of the positive aspects of a traditional histology course. Thus far, course evaluation responses indicate that students enjoy a more efficient laboratory experience.

Re-engineering Colles: Form, function and fragility fractures

Of the twenty nine anatomy professors in the Royal College of Surgeons in Ireland, primus inter pares is Abraham Colles. In his 1811 book A Treatise on Surgical Anatomy he revolutionised the subject by teaching it topographically, seeking "to describe the relative position of the parts and to point out the subservience of anatomical knowledge to surgical practice". Today we have extended this to 'clinical practice' and, in the Anatomy Room, students are guided through each region by clinically trained staff, from surface anatomy via three-dimensional dissection to radiological images. This is augmented by online histology and radiology courses and DVDs in which dissection footage, edited by a content analysis engine, is used to preview and review practical classes. In the same book, Colles also wrote that 'the fixed and immutable laws of mathematics are little applicable to the science of medicine'. Computer-aided learning argues against this. So does research which links fatigue microdamage to bone remodelling and the development of algorithms to predict, and thus prevent, osteoporotic fractures. Mechanical principles are being used to develop scaffolds for tissue engineering and to optimise the mechanical environment of seeded mesenchymal stem cells. While Colles' teaching approach holds true, in biomechanics, tissue engineering and computing, mathematical laws are now being successfully applied to medical science.

Long‐term follow‐up of patients with NAFLD and elevated liver enzymes†‡

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of elevated liver enzymes in patients of developed countries. We determined the long-term clinical and histological courses of such patients. In a cohort study, 129 consecutively enrolled patients diagnosed with biopsy-proven NAFLD were reevaluated. Survival and causes of death were compared with a matched reference population. Living NAFLD patients were offered repeat liver biopsy and clinical and biochemical investigation. Mean follow-up (SD) was 13.7 (1.3) years. Mortality was not increased in patients with steatosis. Survival of patients with nonalcoholic steatohepatitis (NASH) was reduced (P = .01). These subjects more often died from cardiovascular (P = .04) and liver-related (P = .04) causes. Seven patients (5.4%) developed end-stage liver disease, including 3 patients with hepatocellular carcinoma. The absence of periportal fibrosis at baseline had a negative predictive value of 100% in predicting liver-related complications. At follow-up, 69 of 88 patients had diabetes or impaired glucose tolerance. Progression of liver fibrosis occurred in 41%. These subjects more often had a weight gain exceeding 5 kg (P = .02), they were more insulin resistant (P = .04), and they exhibited more pronounced hepatic fatty infiltration (P = .03) at follow-up. In conclusion, NAFLD with elevated liver enzymes is associated with a clinically significant risk of developing end-stage liver disease. Survival is lower in patients with NASH. Most NAFLD patients will develop diabetes or impaired glucose tolerance in the long term. Progression of liver fibrosis is associated with more pronounced insulin resistance and significant weight gain.

Trends in histology laboratory teaching in United States medical schools

Owing to competition for faculty time among the three major missions of today's academic medical centers, as well as the rapid development of computer-based instructional technologies, laboratory instruction in medical schools in the United States has been undergoing dramatic change. In order to determine recent trends in histology laboratory instruction at U.S. medical schools, a detailed Web survey was administered to histology course directors, with about two-thirds of schools responding. The survey was designed to identify trends in the number of hours of histology laboratory instruction that each medical student receives, the amount of faculty effort devoted to histology laboratory instruction, and the use of various computer-based technologies (including virtual microscopy and virtual slides) in histology laboratory instruction. Consistent with the long-term trend of declining total laboratory teaching hours in U.S. medical schools, there is an ongoing reduction in the number of hours of faculty-directed histology laboratory instruction that each medical student receives, with a concomitant reduction in hours of faculty time devoted to histology laboratory instruction. In terms of the tools used in the histology laboratory, there has been a dramatic increase in the use of various forms of computer-aided instruction (including virtual slides). The large increase in the number of schools using computer-aided instruction has not been accompanied by an equivalent decrease in the number of schools that utilize microscopes and glass slides. Rather, the clear trend has been toward a blending of the new computer-based instructional technologies with the long-standing use of microscopes and glass slides.

Natural history and predictors of severity of chronic hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection

Co-infection by the hepatitis C virus (HCV) is observed in up to 30% of HIV-infected individuals. In studies conducted in the 'pre-HAART era', the late consequences of HCV-related chronic liver disease were overshadowed by extra-hepatic causes of deaths, related to severe immune deficiency, and the impact of HCV infection on mortality of HIV-infected patients was low. While the development of HAART has resulted in a significant decrease in morbidity and mortality amongst HIV-infected patients, this clear benefit allowed the expression of liver-related complications associated with HCV chronic infection. The impact of HCV on HIV remains debated but HIV infection significantly modifies the natural history of HCV infection. HIV infection increases levels of HCV viraemia by 2- to 8-fold, resulting in a significant decrease in spontaneous recovery of acute hepatitis. HIV co-infection also worsens the histological course of HCV infection by increasing and accelerating the risk of cirrhosis or leading to rare but lethal fibrosing cholestatic hepatitis. Liver disease is now one of the leading causes of morbidity and mortality in co-infected patients, even if HAART and especially protease inhibitors, may decrease the severity of the liver disease and the liver-related mortality. Several non-exclusive pathogenic processes explain the increasing rate of liver complications associated with HCV-related liver disease.

Do serological tissue turnover markers represent callus formation during fracture healing?

Serological parameters of bone and fibrous tissue turnover were demonstrated to monitor the course of fracture healing. The aim of this study was to evaluate the correlation between the serological parameter levels during fracture healing and callus development in a standardised ovine model of fracture healing. Two years old female sheep received a standardised 3 mm tibial bone defect stabilised by an external fixator. The serological levels of the C-terminal propeptide of procollagen type I (PICP), bone specific alkaline phosphatase (bALP), total alkaline phosphatase (tALP), osteocalcin, tartrate-resistant acid phosphatase (TRAP), calcium, phosphate and the N-terminal peptide of procollagen type III (PIIINP) were observed over a 9-week healing period. The course of fracture healing was monitored radiographically, and the callus composition was evaluated histologically at 2, 3, 6 and 9 weeks post-surgery. The serological results were compared with an untreated control group. Additionally, the maximum values during healing were compared with juvenile values to gauge the level of the serological response. The histological and radiographical results demonstrated callus formation without complications. All serological parameters showed broad inter-individual variations, and the response to the standardised fracture scenario was strongly individual. Maximum values during fracture healing did not reach the juvenile levels. The fractured as well as the control animals showed significant changes in the parameter levels. No correlations were observed between the histological course of healing and the course of bone formation markers whilst the TRAP level was reduced during bony callus formation. The PIIINP level increased when the amount of soft callus tissue decreased during healing. The observed bone formation markers were not suitable as general markers to detect the course of fracture healing, whilst PIIINP was able to reflect soft callus degradation.

Non-Hodgkin's lymphoma presenting as a breast mass in patients with HIV infection: A report of three cases

Breast involvement with non-Hodgkin's lymphoma (NHL) is rare. Patients with AIDS have an increased incidence of NHL, often with high-grade histology, extranodal presentation and aggressive clinical course. Lymphoma of the breast in patients with HIV-1 infection has not been reported. We reviewed our tumor registry database of all AIDS-associated NHL and report on the clinical presentation and long-term outcome of 3 patients with AIDS who presented with lymphomatous involvement of the breast.

Preliminary Results of Immunosuppression With Thymoglobuline Pretreatment and Hepatitis C Virus Recurrence in Liver Transplantation

Induction with thymoglobulin, a potent anti-thymocyte polyclonal antibody, has been recently reported to allow minimization of postoperative immunosuppression in organ transplantation. The relationship with recurrence of hepatitis C virus (HCV) after liver transplantation (LT) has never been investigated. We report herein on the outcome of 22 HCV+ patients receiving thymoglobulin pretreatment and minimal immunosuppression after liver transplantation. Patient survival and acute rejection rates were good, with remarkably low dosages and levels of immunosuppression achieved with thymoglobulin, and without exposing patients to an elevated risk of rejection. A progressive weaning of the primary immunosuppressant was also possible in the majority of patients without complications. The HCV recurrence rate was similar to that reported in the literature, although lower HCV RNA viral loads were obtained with thymoglobulin and a mild histologic course. Although our results need to be validated in large cohort studies, our experience shows that minimization of immunosuppression with thymoglobulin is effective to protect against rejection and demonstrated a positive impact on HCV recurrence that deserves further investigation.

Atypical presentations of solitary fibrous tumors of the central nervous system: an analysis of unusual clinicopathological and outcome patterns in three new cases with a review of the literature

Central nervous system (CNS) solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms recognized less than a decade ago. Approximately 60 cases of SFT have been reported in the central nervous system. We describe three atypical SFTs of the CNS, two intracranial and one within the spine. One intracranial SFT arose from the sella turcica and expanded into the suprasellar areas. It relapsed twice during the 3 years following partial resection, and the MiB 1 labeling index steadily increased without obvious malignant transformation. The second SFT arose from the confluence of the sinuses, widely invaded the lateral sinus and adjacent bones, had a low MiB 1 index and has not recurred after 5 years. The intraspinal tumor occurred at T5-T7 in a patient with multiple café-au-lait spots, was predominantly myxoid and developed a second similar lesion at S3-S5 14 years later. The MiB 1 index was lower in the second tumor. Immunohistochemistry confirmed that all were SFTs. These atypical presentations gave us an opportunity to provide further information about the natural histological course of CNS SFTs.

Minimization of immunosuppression with thymoglobuline pre-treatment and HCV recurrence in liver transplantation

Induction with thymoglobuline, a potent anti-thymocyte polyclonal antibody, has been recently reported to allow minimization of postoperative immunosuppression in organ transplantation. The relationship with recurrence of hepatitis C virus (HCV) after liver transplantation (LTx) has never been investigated. We report here on the outcome in 22 HCV+ patients receiving thymoglobuline pre-treatment and minimal immunosuppression after LTx. Patient survival and acute rejection rates were good, and remarkably low dosages and levels of immunosuppression were achieved with thymoglobuline, without exposing patients to an elevated risk of rejection. A progressive weaning of the primary immunosuppressor was also possible in the majority of patients without complications. The HCV recurrence rate was similar to what is reported in the literature, although lower HCV-RNA viral loads were obtained with thymoglobuline, with a mild histologic course. Although our results need to be validated in large cohort studies, our experience shows that minimization of immunosuppression with thymoglobuline is effective in protecting against rejection and demonstrated a positive impact on HCV recurrence that deserves further investigation.

MMF and Calcineurin Taper in Recurrent Hepatitis C After Liver Transplantation: Impact on Histological Course

Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) is almost universal. The optimal immunosuppression for these patients is still under discussion. We designed a retrospective case-control study to evaluate the effect of mycophenolate mofetil (MMF) treatment in patients with recurrent hepatitis C. Forty patients with histologically proven hepatitis C recurrence after OLT were treated with MMF and calcineurin inhibitor (CNI) taper for 24 months and matched with 40 non-MMF-treated positive liver transplant recipients. Liver biopsies were obtained prior to MMF treatment and after a mean follow-up of 24 months. Histological changes were evaluated utilizing the Metavir score. Comparison of fibrosis/inflammation showed no impairment of histological findings during MMF treatment. In contrast, histological findings of the 40 non-MMF patients showed a significant increase of severity for inflammation/fibrosis. Viral load was similar in both groups. The course of alanin amino transferase (ALT) levels measured during MMF treatment showed a significant decrease. MMF in combination with CNI taper showed a positive effect on fibrosis progression, graft inflammation and ALT levels and may improve the clinical course of HCV after OLT, however, the antiviral properties of MMF are still unconfirmed.

Antibody-Mediated Rejection after Adult ABO-Incompatible Liver Transplantation Remedied by Gamma-Globulin Bolus Infusion Combined with Plasmapheresis

Adult ABO-incompatible liver transplantation has been known to be associated with markedly desperate outcomes. Antibody-mediated rejection (AMR) has been recognized as one of the primary causes of these desperate outcomes, but its clinical features and significance have not been well understood. Recently, some clinicians have succeeded in improving the outcome of adult ABO-incompatible liver transplantation. However, in some transplant patients undergoing these treatments, AMR has still led to graft losses. We recently encountered two patients suffering from AMR after adult ABO-incompatible liver transplantation and remedied their conditions with various therapeutic modalities including direct hepatic infusion therapy and gamma-globulin bolus infusion therapy combined with plasmapheresis. In this article, we describe the clinical features of these patients and the therapeutic strategies we applied. Furthermore, we show the histologic course of the recovery from AMR in the second patient, from whom we were able to extract serial liver biopsies.

The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies

The histological course of nonalcoholic fatty liver disease (NAFLD) remains undescribed. Therefore, we examined the liver histology of NAFLD patients who had undergone sequential liver biopsies. Data on 103 patients who underwent serial liver biopsies in the absence of effective treatment were reviewed, and biopsies scored in a blind fashion. Mean interval between biopsies was 3.2+/-3.0 years (range 0.7-21.3). Fibrosis stage apparently progressed in 37%, remained stable in 34% and regressed in 29%. Severity of steatosis, inflammation, hepatocyte ballooning and Mallory's hyaline improved significantly. Aminotransferases decreased significantly between biopsies, paralleling improvement in steatosis and inflammatory features but not fibrosis stage. The rate of fibrosis change ranged from -2.05 to 1.7 stages/year. By multivariate analysis, diabetes (P = 0.007) and low initial fibrosis stage (P < 0.001) were associated with higher rate of fibrosis progression, as was higher body mass index (P = 0.008) when cirrhotics were excluded. Fibrosis in NAFLD progresses slowly over time with considerable variability in the rate of changes among patients. Changes of aminotransferases do not parallel changes in fibrosis stage. Diabetic patients with elevated BMI and low fibrosis stage are at risk for higher rates of fibrosis progression.

Donor age influences 10-year liver graft histology independently of hepatitis C virus infection

Factors influencing the long-term histological outcome of liver graft are not known. We conducted a prospective study based on a 10-year liver biopsy in order to identify the main factors influencing long-term graft histology. 270 of 423 patients who still had their first functional graft 10 years after liver transplantation accepted to undergo routine liver biopsy. All slides were blindly reviewed by two pathologists. Main histological findings were fibrosis in 143 patients (54%) and ductopenia in 76 patients (29%). Ductopenia was independently related to higher donor age (32+/-12 vs 28+/-13 years; P<0.02). Severity of fibrosis was influenced by hepatitis C virus (HCV) infection (P<0.001), hepatitis B virus (HBV) recurrence (P=0.001) and higher donor age (P=0.03). Eighty biopsies (30%) showed minimal-change lesions which were associated with the absence of HCV infection (24/80 vs 99/185; P<0.001) or of HBV infection (1/80 vs 15/185; P=0.03) and lower donor age (25+/-11 vs 31+/-13 years; P<0.001). Post-transplant infection by HCV or HBV are main factors influencing the histological course of liver graft. Donor age was also a strong factor in HCV infected patients as well as in HCV-negative patients. This variable should be taken into account, particularly for candidate recipients with long life expectancy.

Increasing active student participation in histology.

As have many institutions, the New York University School of Medicine (NYUSM) has instituted curriculum revisions that allow for increased independent study but impose significant time constraints on laboratory courses. Challenged by decreased laboratory time, we sought creative solutions for our histology course, "Cell Biology of Tissues and Organs," using computer- and Web-based materials. While these solutions have facilitated independent study, they have not fostered the subtler lessons learned in the laboratory, such as communication skills and team approaches to learning. To retain these elements and enrich our course, we focused on increasing student participation in the laboratory through unit reviews presented by students, student-generated comprehensive reviews, and practice exams. The active engagement of students in the learning process has resulted in a more exciting laboratory experience for all.

Coalition of American societies for anatomy

On 17 October 2003, there was a historic meeting in Washington, D.C. Representatives from the American Association of Anatomists (AAA; Robert McCuskey, President; Kathy Svoboda, President-Elect; and Andrea Pendleton, Executive Director), American Association of Clinical Anatomists (AACA; Daniel Graney, Past-President; Arthur Dalley, Past-President; and Todd R. Olson, Treasurer), Association of Anatomy, Cell Biology, and Neurobiology Chairpersons (AACBNC; James West, President-Elect; and Stephen Carmichael, Past-President), and the Human Anatomy and Physiology Society (HAPS; Phil Tate, President; Sandra Lewis, President-Elect; and Gail Jenkins, Treasurer) gathered in a roundtable discussion hosted by Donald Jenkins of the National Library of Medicine. The meeting was the initiative of Bob McCuskey and enthusiastically endorsed by the representatives of the above-named organizations. The goal was to seek common ground on challenges and opportunities presented to the modern anatomist in the United States and Canada. The discussions were amicable and far-reaching. There was widespread concern about the source of future teachers of anatomy. Whereas the participants unanimously agreed that a shortfall is predictable, it is imperative to involve the lead administrators at the involved academic institutions (i.e., medical school deans). Bob McCuskey will organize leaders of the involved organizations, as well as a leader from the Council of Deans (a subgroup of the Association of American Medical Colleges), to draft a “white paper” on the importance of anatomy in health education, the shortage of anatomy educators, and the need to train qualified educators for the future. The use of donated human bodies for the purpose of education was another topic of discussion. It was agreed that recognition and appreciation of this precious resource is a preeminent concern to all anatomists. Also, public displays of human material need to conform to local laws and the sensibilities of the general community must be considered. Representatives from each of the societies will work together to address common concerns about donated material. Don Jenkins moderated the discussion in such a way that each participant had the opportunity to express his or her opinions fully, and each topic was thoroughly covered before moving onto another. Topics were as diverse as forming a coalition of health professionals who constitute the “end users” of anatomy education, to the future of virtual microscopy (the use of computers rather than microscopes) in histology courses. Each participant had ample opportunity to hear the opinions of others and to be heard. Mutual respect among the participants was abundant. Although historical differences among some of the organizations were reviewed, it was obvious that we are entering a new era of cooperation among anatomists. Several joint projects are already in place and more will be organized in the near future. As testament to this newly forged alliance, the AAA, AACA, and HAPS agreed to form an umbrella organization that will provide a forum for discussion and subsequently coordination of the common causes of anatomical organizations in the United States and Canada. This organization will be known as the Coalition of American Societies for Anatomy (CASA; a homey acronym, to be sure). We are predicting success for this newly formed coalition.

Teaching medical histology at the University of South Carolina School of Medicine: Transition to virtual slides and virtual microscopes.

We describe how the histology course we teach to first-year medical students changed successfully from using glass slides and microscopes to using virtual slides and virtual microscopes. In 1988, we taught a classic medical histology course. Subsequently, students were loaned static labeled images on projection slides to introduce them to their microscope glass slides, and we made laser disks of histological images available in the teaching lab. In 2000, we placed the static labeled images and laboratory manual on the Web. We abandoned the Web-based approach in 2001. Faculty selected specific areas on microscope glass slides in student collections for scanning at a total magnification of 40, 100, 200, or 400. Christopher M. Prince of Petro Image, LLC, scanned the glass slides; digitized, encoded, and compressed (95%) the images; and placed them on CD-ROMs. The scanned images were viewed up to a magnification of 400 using the MrSID viewer (LizardTech software) and the computer as a virtual microscope. This viewer has many useful features, including effective microscope and telescope functions that provide greater versatility for sample study and speed in localizing structures than was possible with the actual microscope. Image detail is indistinguishable from that viewed under the light microscope at equivalent magnifications. Static labeled images were also placed on CD-ROMs to introduce students to the virtual slides. Students could view all the images on their CD-ROMs at any time and in any place with their laptop computers without going online. Students no longer rented light microscopes in 2002. Both students and faculty have shown strong support for using this approach to teaching histology during the past 2 years.