The pathology student fellowship program at the University of Vermont: 1956-2005

Student fellowship programs in pathology offer a unique educational experience for selected medical students. In this report, the specialty preferences of former student fellows graduating from the University of Vermont were analyzed. Since 1956, 110 students have participated in this program, of whom 33 chose pathology as a career. These individuals represented 32.6% of all Vermont graduates who entered pathology between 1958 and 2005. In addition, former student fellows were more likely to become academic pathologists and to obtain subspecialty certification. Furthermore, based on comments received from former student fellows, the program had a positive impact on the medical education and career of pathologists and nonpathologists alike. It is concluded that student fellowship programs represent a powerful recruitment tool for pathology generally and for academic pathology in particular. The development of a database to track these programs and their graduates is essential to fully assess the educational impact of pathology student fellowship programs nationally.     

Attenuation correction for small animal SPECT imaging using x-ray CT data

Photon attenuation in small animal nuclear medicine scans can be significant when using isotopes that emit lower energy photons such as iodine-125. We have developed a method to use microCT data to perform attenuation corrected small animal single-photon emission computed tomography (SPECT). A microCT calibration phantom was first imaged, and the resulting calibration curve was used to convert microCT image values to linear attenuation coefficient values that were then used in an iterative SPECT reconstruction algorithm. This method was applied to reconstruct a SPECT image of a uniform phantom filled with 125I-NaI. Without attenuation correction, the image suffered a 30% decrease in intensity in the center of the image, which was removed with the addition of attenuation correction. This reduced the relative standard deviation in the region of interest from 10% to 6%.     

Diminished neo-antigen response to keyhole limpet hemocyanin (KLH) vaccines in patients after treatment with chemotherapy or hematopoietic cell transplantation

Relapse is the most common cause of treatment failure for advanced cancer, even those treated with autologous hematopoietic cell transplantation (HCT). Effective tumor-specific immunotherapy may decrease relapse, however, this will fail if the immune system is unable to respond. We developed a strategy to test immune responses with a single injection of the bona fide neo-antigen KLH. The model was first tested in 37 normal volunteers using three KLH vaccines: Intracel KLH, Biosyn KLH, and Biosyn KLH + adjuvant. Despite finding the immunogenic epitope conserved in both products, intact Intracel KLH induced a better response compared to a purified 350/390 kDA subunit of KLH contained in the Biosyn KLH product. Addition of a synthetic oil adjuvant (Montanide ISA51) restored the response to a single injection of Biosyn KLH. A quantitative readout measured by a KLH-specific cellular and humoral response with isotype switching 1 month after KLH vaccination was established. To test the integrity of the adaptive immune response in cancer patients, we vaccinated 14 patients post-HCT and 19 patients with advanced cancer with KLH vaccines that elicited a 100% response rate in normal volunteers. In marked contrast to normal subjects, both responses were significantly impaired up to 16 months after autologous HCT with an intermediate response in advanced cancer patients. KLH vaccines are safe and require only a single injection to test neo-antigen responses providing an optimal platform for definitive testing of strategies to improve diminished immune recovery after chemotherapy or post-HCT.     

Some principles of regeneration in mammalian systems

This article presents some general principles underlying regenerative phenomena in vertebrates, starting with the epimorphic regeneration of the amphibian limb and continuing with tissue and organ regeneration in mammals. Epimorphic regeneration following limb amputation involves wound healing, followed shortly by a phase of dedifferentiation that leads to the formation of a regeneration blastema. Up to the point of blastema formation, dedifferentiation is guided by unique regenerative pathways, but the overall developmental controls underlying limb formation from the blastema generally recapitulate those of embryonic limb development. Damaged mammalian tissues do not form a blastema. At the cellular level, differentiation follows a pattern close to that seen in the embryo, but at the level of the tissue and organ, regeneration is strongly influenced by conditions inherent in the local environment. In some mammalian systems, such as the liver, parenchymal cells contribute progeny to the regenerate. In others, e.g., skeletal muscle and bone, tissue-specific progenitor cells constitute the main source of regenerating cells. The substrate on which regeneration occurs plays a very important role in determining the course of regeneration. Epimorphic regeneration usually produces an exact replica of the structure that was lost, but in mammalian tissue regeneration the form of the regenerate is largely determined by the mechanical environment acting on the regenerating tissue, and it is normally an imperfect replica of the original. In organ hypertophy, such as that occurring after hepatic resection, the remaining liver mass enlarges, but there is no attempt to restore the original form.     

Home-based video CBT for comorbid geriatric insomnia: a pilot study using secondary data analyses

Two recent studies showed that cognitive-behavioral treatment (CBT) is efficacious in treating insomnia in older adults with comorbid medical conditions. The authors extended these findings by comparing 12 older adults with comorbid insomnia who received a home-based video CBT program to the authors' previously published data on 24 participants who received classroom CBT or no treatment. All 36 participants were initially randomized within the same protocol, but the video arm was conducted 7 months after completion of the other two study arms. Compared to controls, the video CBT group demonstrated significant changes in five of eight self-report measures of sleep at posttreatment, including sleep latency, time awake after sleep onset, total time in bed, overall sleep quality, and dysfunctional beliefs and attitudes about sleep. Compared to controls, the video CBT group also had posttreatment improvements in daytime functioning, including mood, pain perception, social functioning, and energy-vitality. Although video CBT was not significantly different from classroom CBT on self-report measures, the attrition rate was higher (27% vs. 19%) and the number of participants who achieved clinically significant change was lower (50% vs. 73%). These preliminary findings suggest that delivering CBT in a home-based video format has the potential to serve as a first-line, cost-effective treatment for comorbid insomnia.     

Radiofrequency Ablation of Uterine Fibroids: a Review

Laparoscopic, ultrasound-guided radiofrequency ablation (RFA) is a new, FDA-cleared uterine sparing, outpatient procedure for uterine fibroids. The procedure utilizes recent technological advancements in instrumentation and imaging, allowing surgeons to treat numerous fibroids of varying size and location in a minimally invasive fashion. Early and mid-term data from multi-center clinical trials have demonstrated safety and efficacy, with resolution or improvement of symptoms and significant volume reduction. Re-intervention rates for fibroid symptoms have been low. The procedure is well tolerated with a typically uneventful and rapid recovery requiring NSAIDs only for postoperative pain. While post RFA pregnancy data are limited, the results are promising.     

Maternal and feto-placental phenotypes of early-onset severe preeclampsia

Objective: To characterize maternal and feto-placental phenotypes of severe preeclampsia that trigger early-onset delivery.

Methods: A retrospective cohort review of pregnant women receiving care from 2000 to 2010. Subjects with early-onset severe preeclampsia delivering between 20 and 32 weeks were identified excluding multiple gestations or major anomalies. We defined indications for delivery as maternal (i.e. severe headache or abnormal laboratory parameters), feto-placental (i.e. non-reassuring tracing) or mixed (i.e. both maternal and feto-placental factors). To characterize the groups, demographic, clinical, laboratory, ultrasound and pathology data were abstracted. Statistical analysis was conducted.

Results: We identified 164 subjects meeting inclusion criteria. Indications for delivery were maternal (57.3%), feto-placental (29.9%) or mixed (12.8%). Compared to neonates delivered for maternal indications, birthweight was significantly lower among neonates delivered for feto-placental or mixed indications (p?<?0.001). While placental findings were largely similar between groups, abnormal cord insertion was more common in subjects delivered for feto-placental factors (p?=?0.02). Women delivered for maternal indications had more significant lab abnormalities than women delivered for feto-placental or mixed indications.

Conclusion: In attempting to classify early-onset severe preeclampsia by delivery indication, we found patterns to suggest that feto-placental and maternal phenotypes of disease may have distinct pathophysiologic underpinnings.     

Stability of MCT/LCT‐Based Total Nutrient Admixtures for Neonatal Use Over 30 Hours at Room Temperature

Background: United States Pharmacopeial Chapter <729> places a limit on the percentage of large fat globules >5 µm, expressed as a PFAT5 of <0.05% for all native lipid emulsions. Some adult total nutrient admixtures (TNAs) have also remained below this limit for up to 48 hours. In 2003, medium‐chain/long‐chain triglyceride (MCT/LCT)–based neonatal TNAs with between 2% and 3% amino acid (AA) concentrations were shown to be similarly stable by the PFAT5 parameter. Stability assessment of neonatal TNAs with AA <2% or ≥3% were tested. Methods: Eight neonatal TNAs with various combinations of AA (1%, 1.5%, 3%, and 4%), glucose (G; 5% and 10%), and MCT/LCT (ML; 2% and 4%) and standard concentrations of additives were tested in triplicate (n = 24) over 30 hours (immediately after mixing, then at 6, 24, and 30 hours) at 25°C ± 2°C. PFAT5 determinations for all 24 formulations were made in duplicate, immediately after mixing, and then at 6, 24, and 30 hours later. Mean droplet size (MDS) and pH were assessed at the outset and end of the study. Results: The differences in the PFAT5 levels were significant (P < .001) by a 2‐way analysis of variance based on formula and time as the independent variables. The TNAs with 1% and 1.5% AA with all Gs and MLs (group 1, n = 12) had PFAT5 levels >0.05% (up to 0.50%) in most samples (68 of 96 samples, or 71% of cases) in the study, whereas in the same TNAs, but made with 3% and 4% AA (group 2, n = 12), 100% of samples (all 96 cases) had PFAT5 levels <0.05% (up to 0.04%), and this difference was significant (P < .001). Pairwise comparisons between groups based on overall values of PFAT5, MDS, and pH showed significant differences between groups for all variables. Conclusions: For neonatal TNAs, AA level is the most sensitive determinant of stability, and the PFAT5 parameter is the most sensitive indicator of stability.