The rat mammary gland: morphologic changes as an indicator of systemic hormonal perturbations induced by xenobiotics

The development and morphology of the rat mammary gland are dependent upon several hormones including estrogens, androgens, progesterone, growth hormone and prolactin. In toxicology studies, treatment with xenobiotics may alter these hormones resulting in changes in the morphology of reproductive tissues such as the mammary gland. In the rat, male and female mammary glands exhibit striking morphologic differences that can be altered secondary to hormonal perturbations. Recognizing these morphologic changes can help the pathologist predict potential xenobiotic-induced perturbations in the systemic hormonal milieu. This review examines the development of the rat mammary gland and the influence of sex hormones on the morphology of the adult male and female rat mammary gland. Specific case examples from the literature and data from our laboratory highlight the dynamic nature of the rat mammary gland in response to hormonal changes.     

Residents feel unprepared and unsupervised as leaders of cardiac arrest teams in teaching hospitals: a survey of internal medicine residents

OBJECTIVE: We aimed to determine internal medicine residents' perceptions of the adequacy of their training to serve as in-hospital cardiac arrest team leaders, given the responsibility of managing acutely critically ill patients and with recent evidence suggesting that the quality of cardiopulmonary resuscitation provided in teaching hospitals is suboptimal. DESIGN: Cross-sectional postal survey. SETTING: Canadian internal medicine training programs. PARTICIPANTS: Internal medicine residents attending Canadian English-speaking medical schools. INTERVENTIONS: A survey was mailed to internal medicine residents asking questions relating to four domains: adequacy of training, perception of preparedness, adequacy of supervision and feedback, and effectiveness of additional training tools. MEASUREMENTS AND MAIN RESULTS: Of the 654 residents who were sent the survey, 289 residents (44.2%) responded. Almost half of the respondents (49.3%) felt inadequately trained to lead cardiac arrest teams. Many (50.9%) felt that the advanced cardiac life support course did not provide the necessary training for team leadership. A substantial number of respondents (40%) reported receiving no additional cardiac arrest training beyond the advanced cardiac life support course. Only 52.1% of respondents felt prepared to lead a cardiac arrest team, with 55.3% worrying that they made errors. Few respondents reported receiving supervision during weekdays (14.2%) or evenings and weekends (1.4%). Very few respondents reported receiving postevent debriefing (5.9%) or any performance feedback (1.3%). Level of training and receiving performance feedback were associated with perception of adequacy of training (r(2) = .085, p < .001). Respondents felt that additional training involving full-scale simulation, leadership skills training, and postevent debriefing would be most effective in increasing their skills and confidence. CONCLUSIONS: The results suggest that residents perceive deficits in their training and supervision to care for critically ill patients as cardiac arrest team leaders. This raises sufficient concern to prompt teaching hospitals and medical schools to consider including more appropriate supervision, feedback, and further education for residents in their role as cardiac arrest team leaders.     

Osseointegrated implants in craniofacial application: current status

The success rates of craniofacial osseointegrated implants are not uniform throughout the craniofacial area. A better understanding of their clinical behaviour is needed. This article investigates current perspectives on the application of endosseous implants in the restoration of craniofacial defects. An online search was completed for the time period from 1966 to 2007, along with a manual search, to locate relevant peer-reviewed articles and textbooks published in English. A review of published reports of craniofacial application of endosseous implants in irradiated and nonirradiated tissue sites showed a strong correlation between anatomic sites and clinical success. Maxillofacial prosthetic considerations are also reviewed.     

Robotic Resection of Type I Hilar Cholangiocarcinoma with Intrapancreatic Bile Duct Dissection

Background

Type I hilar cholangiocarcinoma is a malignancy of the extrahepatic bile duct for which margin-negative resection with sufficient lymphadenectomy may provide curative treatment. The aim of this video is to highlight the advantages of optical magnification, articulating instruments, and indocyanine green fluorescent cholangiography to demonstrate extrahepatic bile duct resection from the biliary confluence to the intrapancreatic bile duct with comprehensive hilar lymphadenectomy for pathologic staging.

Methods

A 58-year-old male presented with obstructive jaundice and was found to have a biliary stricture arising from the cystic duct and bile duct junction. Endoscopic biopsy of the bile duct confirmed adenocarcinoma. His case was presented at a multidisciplinary tumor conference where consensus was to proceed with upfront robotic en bloc extrahepatic bile duct resection with hilar lymphadenectomy and Roux-en-Y hepaticojejunostomy.

Results

Final pathology demonstrated margin-negative resection of moderately differentiated adenocarcinoma, 1 out of 12 lymph nodes involved with disease, and pathologic stage T2N1M0 (stage IIIC). The patient had no postoperative complications and was discharged home on postoperative day 5. At 6 weeks from his operative date, he was initiated on four cycles of adjuvant gemcitabine/capecitabine, followed by 50 Gray external beam radiation therapy with capecitabine, then four cycles of gemcitabine/capecitabine, completed after 6 months of therapy.

Conclusions

Robotic extrahepatic bile duct resection, hilar lymphadenectomy, and biliary enteric reconstruction is feasible and should be considered for selected cases of bile duct resection.

     

Modest rates and wide variation in timely access to repeat kidney transplantation in the United States

Success of transplantation is not limited to initial receipt of a donor organ. Many kidney transplant recipients experience graft loss following initial transplantation and the benefits of expedited placement on the waiting list and retransplantation extend to this population. Factors associated with access to repeat transplantation may be unique given experience with the transplant process and prior viability as a candidate. We examined the incidence, risk factors, secular changes, and center‐level variation of preemptive relisting or transplantation (PRLT) for kidney transplant recipients in the United States with graft failure (not due to death) using Scientific Registry of Transplant Recipients data from 2007 to 2018 (n = 39 557). Overall incidence of PRLT was 15% and rates of relisting declined over time. Significantly lower PRLT was evident among patients who were African American and Hispanic, males, older, obese, publicly insured, had lower educational attainment, were diabetic, had longer dialysis time prior to initial transplant, shorter graft survival, longer distance to transplant center, and resided in distressed communities. There was significant variation in PRLT by center, median = 13%, 10th percentile = 6%, 90th percentile = 24%. Cumulatively, results indicate that despite prior access to transplantation, incidence of PRLT is modest with pronounced clinical, social, and center‐level sources of variation suggesting opportunities to improve preemptive care among patients with failing grafts.     

A Meta‐Analysis of the Association of Fracture Risk and Body Mass Index in Women

Several recent studies suggest that obesity may be a risk factor for fracture. The aim of this study was to investigate the association between body mass index (BMI) and future fracture risk at different skeletal sites. In prospective cohorts from more than 25 countries, baseline data on BMI were available in 398,610 women with an average age of 63 (range, 20–105) years and follow up of 2.2 million person‐years during which 30,280 osteoporotic fractures (6457 hip fractures) occurred. Femoral neck BMD was measured in 108,267 of these women. Obesity (BMI ≥ 30 kg/m²) was present in 22%. A majority of osteoporotic fractures (81%) and hip fractures (87%) arose in non‐obese women. Compared to a BMI of 25 kg/m², the hazard ratio (HR) for osteoporotic fracture at a BMI of 35 kg/m² was 0.87 (95% confidence interval [CI], 0.85–0.90). When adjusted for bone mineral density (BMD), however, the same comparison showed that the HR for osteoporotic fracture was increased (HR, 1.16; 95% CI, 1.09–1.23). Low BMI is a risk factor for hip and all osteoporotic fracture, but is a protective factor for lower leg fracture, whereas high BMI is a risk factor for upper arm (humerus and elbow) fracture. When adjusted for BMD, low BMI remained a risk factor for hip fracture but was protective for osteoporotic fracture, tibia and fibula fracture, distal forearm fracture, and upper arm fracture. When adjusted for BMD, high BMI remained a risk factor for upper arm fracture but was also a risk factor for all osteoporotic fractures. The association between BMI and fracture risk is complex, differs across skeletal sites, and is modified by the interaction between BMI and BMD. At a population level, high BMI remains a protective factor for most sites of fragility fracture. The contribution of increasing population rates of obesity to apparent decreases in fracture rates should be explored. © 2014 American Society for Bone and Mineral Research.     

“Brown Bag” Simulations to Teach Drug Utilization Review

Objective. To teach drug utilization review (DUR) skills to pharmacy students and assess their abilities and confidence before and after training.Design. Profile reviews and online and live drug-utilization-review activities of increasing difficulty were incorporated into the first (P1), second (P2), and third (P3) years of the Pharmacy Skills Training Laboratory sequence in a doctor of pharmacy (PharmD) curriculum.Assessment. An online survey instrument was administered to gauge how comfortable students were with specific DUR skills before and after the activities. Students’ confidence in performing specific DUR skills improved after completing the activities.Conclusion. Profile reviews, as well as online and live medication reviews, gave students numerous opportunities to practice drug utilization review skills throughout the first 3 years of the pharmacy curriculum. Students’ confidence in performing specific drug utilization review skills improved after the activities. Students’ ability to perform the skills also improved as measured with the developed checklist in section V and VI of the Pharmacy Skills Laboratory sequence.     

Quantification of spread of cerebellar long-term depression with chemical two-photon uncaging of glutamate

Localized, chemical two-photon photolysis of caged glutamate was used to map the changes in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors caused by long-term synaptic depression (LTD) in cerebellar Purkinje cells. LTD produced by pairing parallel fiber activity with depolarization was accompanied by a decline in the response of Purkinje cells to uncaged glutamate that accounted for both the time course and magnitude of LTD. This depression of glutamate responses was observed not only at the site of parallel fiber stimulation but also at more distant sites. The amount of LTD decreased with distance and was half-maximal 50 microm away from the site of parallel fiber activity. Estimation of the number of parallel fibers active during LTD induction indicates that LTD modified glutamate receptors not only at active synapses but also at 600 times as many inactive synapses on a single Purkinje cell. Therefore, both active and inactive parallel fiber synapses can undergo changes at a postsynaptic locus as a result of associative pre- and postsynaptic activity.