Gary L. Kolesari

Human anatomical science and illustration: the origin of two inseparable disciplines.

From the early wall paintings of ancient Egyptians to the recent advent of computer graphics, medical illustrators have employed a variety of techniques and materials to enrich the art of medicine. Over the centuries, medical illustrators have captured the variety of physical findings observed in the clinical, surgical, or postmortem settings and transferred them to a permanent medium. Specifically, the study of human anatomy has enjoyed a historically popular courtship with medical artistry since 1543, when Andreas Vesalius published his now legendary work entitled De Humani Corporis Fabrica. However, the development and subsequent advancement of human anatomical illustration are indebted to individuals whose lifetimes span several centuries prior to Vesalius. The scientific achievements in anatomy manifest not only an advancement of knowledge, but also are a reflection of cultural, political, and religious beliefs. With respect to the development of human anatomic illustration, three elements were essential: the recognition of anatomy as a distinct branch of medical science, the acceptance of human dissection as a scientific method to advance understanding of anatomical structure, and the advancement in printing such that illustrations could be included alongside descriptive text. This brief study will examine these milestones while highlighting the origin of anatomical illustration in its historical context and its relationship to the development of human anatomy as a recognized medical science. Clin. Anat. 12:120–129, 1999.

Cardiovascular teratogenicity of terbutaline and ritodrine in the chick embryo

OBJECTIVE We determined the teratogenic effects of terbutaline and ritodrine, both beta 2-sympathomimetic agonists, on the stage 24 (4-day) chick embryo. STUDY DESIGN We used a topical method of application of terbutaline or ritodrine to the stage 24 chick embryo in ovo. Doses of terbutaline ranged from 5.5 x 10(-10) to 6.5 x 10(-9) mol per embryo, and ritodrine doses ranged from 4.6 x 10(-11) to 4.6 x 10(-8) mol per embryo. To further determine the pharmacologic nature of the teratogenic potential of terbutaline or ritodrine, the experiments were repeated after pretreatment with butoxamine hydrochloride, a preferential beta 2-antagonist, or metoprolol tartrate, a preferential beta 1-antagonist, 4 hours before application of terbutaline or ritodrine. RESULTS Terbutaline treatment was associated with significantly higher rates of anomalies than in controls at all dosages used, whereas ritodrine induced significantly more anomalies at or above doses of 4.6 x 10(-9) mol per embryo. At an equimolar dose pretreatment with butoxamine hydrochloride significantly reduced the cardiovascular teratogenic effects of terbutaline and ritodrine. Pretreatment with metoprolol tartrate at any dose did not significantly reduce terbutalines potential. Metoprolol, at doses tenfold or 100-fold higher than ritodrine, was able to significantly reduce the teratogenic effects of ritodrine. CONCLUSIONS Our data suggest that terbutaline and ritodrine are teratogenic in the chick and that these agents exert their teratogenic effects primarily through stimulation of the beta 2-adrenergic receptor.

Computerized Grading of Anatomy Laboratory Practical Examinations

At the Medical College of Wisconsin, a procedure was developed to allow computerized grading and grade reporting of laboratory practical examinations in the Clinical Human Anatomy course. At the start of the course, first year medical students were given four Lists of Structures. On these lists, numbered items were arranged alphabetically; the items were anatomical structures that could be tagged on a given lab practical examination. Each lab exam featured an anatomy laboratory component and a computer laboratory component. For the anatomy lab component, students moved from one question station to another at timed intervals and identified tagged anatomical structures. As students identified a tagged structure, they referred to a copy of the list (provided with their answer sheet) and wrote the number corresponding to the structure on their answer sheet. Immediately after the anatomy lab component, students were escorted to a computer instruction laboratory where they typed their answer numbers into a secured testing component of a learning management system that recorded their answers for automatic grading. After a brief review of examination scores and item analysis by faculty, exam scores were reported to students electronically. Adding this brief computer component to each lab exam greatly reduced faculty grading time, reduced grading errors and provided faster performance feedback for students without changing overall student performance. Anat Sci Ed 1:220–223, 2008.

FGF-2-induced imbalance in early embryonic heart cell proliferation : A potential cause of late cardiovascular anomalies

BACKGROUND This laboratory previously demonstrated that placement of fibroblast growth factor-2 (FGF-2)-soaked beads adjacent to the developing ventricle at stage 24 caused cardiovascular anomalies by embryonic day 15. We sought to characterize early cellular changes that may suggest mechanisms for the abnormalities observed at day 15. Because levels of both myocyte proliferation and immunohistochemically detectable endogenous FGF-2 begin to decline before stage 24 in untreated embryos, it was of interest to determine whether exogenous FGF-2 might maintain cardiac myocyte proliferation at or near peak levels. METHODS Chick embryos were incubated to stage 18 (2.8 days), at which time beads soaked in phosphate-buffered saline (PBS) or 100 microg/ml FGF-2 were placed adjacent to the developing ventricle and development was allowed to continue. After 3 days (stage 29), bromodeoxyuridine (BrdU) was applied to mark dividing cells, followed by double fluorescent assessments to detect relative numbers of dividing and nondividing cells. RESULTS Quantitative image analysis, using Metamorph software, showed that exogenous FGF-2 caused a 62% increase in the overall number of dividing cells (P < 0.01), concomitant with a 25% increase in total cell number (cell density: P < 0.05). Expressed in relative terms, these changes corresponded to a 25% increase in the proliferation labeling index: 30% of all cells were proliferating in FGF-treated hearts, in contrast with only 24% in control hearts. CONCLUSIONS Taken together, these data suggest that an FGF-induced imbalance in myocardial cell proliferation at early developmental stages of heart development causes cardiovascular anomalies during late embryogenesis.

Postmortem blood tests for HIV, HBV, and HCV in a body donation program

A retrospective analysis of the results of blood tests conducted on body donors received by the Anatomical Gift Registry of the Medical College of Wisconsin (MCW) was performed. Over the 5‐year period from April 1992 through March 1997 a total of 785 body donors were tested for Human Immunodeficiency Virus (HIV) and Hepatitis B and C Viruses (HBV and HCV). Eighteen of the 785 donors (2.3%) tested positive for one of these infectious agents. Two donors were positive for HIV, six were positive for HBV and ten were positive for HCV. The death certificates and files of those donors who tested positive were reviewed and the results are presented here. Blood testing prior to the use of the body donors is an effective and reasonable way of identifying the presence of these infectious agents, thus reducing the risk to those who work with cadavers. The cost for the testing at MCW is about

Microbubble contrast imaging of the cardiovascular system of the chick embyro.

60 per donor. Clin. Anat. 11:250–252, 1998.

ESR measurement of dissolved oxygen in 4-day chick embryo blood

Ultrasound imaging of the chick embryo cardiovascular system is limited to B-scan and Doppler technologies. This study demonstrates microbubble contrast imaging of the embryonic cardiovascular anatomy and physiology. Day 8-19 (Hamburger & Hamilton Stage 34-43) chick embryos are examined in ovo using high-frequency ultrasound imaging through an opening in the blunt end (air cell) of the egg. A chorioallantoic vein is cannulated, and small boluses of octofluoropropane lipid microspheres (Definity®) are injected to visualize the chick embryo cardiovascular system. The entire chick embryo cardiovascular system including the two embryologic arteriovenous (AV) shunts can be visualized. More accurate physiologic measurements of ejection fractions and cardiac output measurements can be obtained using this technology. Microbubble contrast ultrasound imaging in the chick embryo greatly expands the ability to study cardiovascular development. Also, the two natural embryonic A-V shunts provide an excellent model to study the bioeffects of microbubbles in the arterial system.

The antiteratogenic effects of hypo- and hyperthermia in trypan blue-treated chick embryos

The magnetic interactions between dissolved oxygen molecules and nitroxide radical spin probes lead to broadening of electron spin resonance (ESR) lines. Based on this property we described an ESR methodology to measure PO2 values in 4-day chick embryo and adult human blood. The total blood volume required for the measurement was only 9 microliter. Using this method PO2 for adult human mixed venous blood was found to be 36.7 mmHg. This is within the established clinical range of 25-40 mmHg for mixed venous blood PO2. The range of mean PO2 values for 4-day chick embryo blood was 27.3- 35.0 mmHg. This is the first time that PO2 values have been reported for individual chick embryos at such an early stage.

Teratogenic effects of implanting fibroblast growth factor-2-soaked beads in the cardiac region of the stage 24 chick embryo.

Fertile White Leghorn chicken eggs (N = 174) were incubated under optimum conditions until the embryos had reached Hamburger-Hamilton stage 12 (about 48 hr). At that time, 20 μl of 1% trypan blue solution, dissolved in 0.85% NaCl (wt/vol) was injected through the yolk sac into the liquid yolk found just under the embryo. After injection, the eggs were separated into groups and returned to the incubator under control conditions (38°C), or at temperatures lower (35°C) or higher (41°C) than optimum. After an additional 24 hr of incubation, the embryos incubated at 35°C (N = 53) exhibited significantly fewer caudal hematomas (P < 0.02) than did embryos incubated at 38°C (N = 51). Similarly, embryos incubated at 41°C (N = 40) also exhibited significantly fewer caudal hematomas (P < 0.05) than did their corresponding (38°C) controls (N = 30). There was no significant difference between the 35°C group and their controls, or the 38°C group and their controls, in embryonic dry weight, dry weight of the area vasculosa, or crown-rump length. The only other significant difference detected between groups was a very slight but significant (P < 0.0005) decrease in Hamburger-Hamilton stage (0.4 stage unit) between embryos incubated at 35°C and the corresponding controls. Since incubation temperatures either above or below optimum result in a marked reduction in the teratogenic response to trypan blue treatment, we conclude that there exists a temperature optimum for the development of caudal hematomas.

Tissue and plasma levels of a teratogenic dose of dopamine in the chick embryo following pretreatment with metoprolol or phosphate buffered saline

The identification of fibroblast growth factor-2 (FGF-2), and other family members, in a variety of embryonic tissue extracts has implicated these growth factors as participants in many embryonic events, including cardiogenesis. The present study was conducted in an attempt to characterize the effects of exogenous FGF-2 on the development of the avian heart. Heparin acrylic beads, each soaked in 100 micrograms/ml FGF-2, were applied to the Hamburger and Hamilton [(1951) J. Morphol. 88:49-92] stage 24 (day 4 of incubation) chick heart, near the primitive ventricle. The embryos were allowed to develop until stage 41 (day 15), at which time they were observed for the presence of gross external and internal anomalies. Crown rump length (CRL), wet weight (WW), and various heart measurements were obtained and compared. The survival rate of the control group was significantly higher (P < 0.05) than that for the experimental group and the anomaly rate for the control group was significantly lower (P < 0.01) than that for the experimental group. The experimental group exhibited a wide range of anomalies, most of which were cardiac in nature; however, anomalies of the ventral thoracoabdominal wall were also noted. Our data suggest that application of exogenous FGF-2 has teratogenic effects on cardiac development as well as on the development of the ventral body wall of the avian embryo.