Infants can breathe and swallow at the same time?

The concept that infants can breathe and swallow simultaneously due to distinct breathing and swallowing channels was propagated primarily by Edmund Crelin and his student, Jeffrey Laitman. Our evaluation of the primary research article that supported this concept found the article to be unconvincing due to numerous misrepresentations of prior data as well as those presented in the article. Despite clear evidence that newborns cannot breathe and swallow simultaneously, Crelin and Laitman continued to support this concept well into the 21st century, which resulted in the concept becoming imbedded in popular literature and the internet, with potentially significant negative clinical consequences. We suggest that a partial explanation why this anatomically and physiologically illogical concept was able to propagate is the paucity of the teaching of newborn anatomy to medical professionals.

Newborn anatomy.

Newborn anatomy, despite being distinctly different than adult anatomy, does not constitute a major component of a typical medical school course in gross anatomy. Accordingly, there is a perception that other than the well-known late 20th-century atlas and small textbook by Edmund Crelin on newborn anatomy, there is almost no information available for anatomists and clinicians to refer to on normal infant anatomy. This perception, as verbalized by Crelin in his books, is not correct. There is an amazing wealth of accurate descriptive and pictorial information on infant anatomy available from late 19th- and early 20th-century sources. One of these sources is a comprehensive 200-page chapter on pediatric anatomy by Richard Scammon that was published in 1923 and that is freely available. Because of some inconsistencies and inaccuracies we have identified in the Crelin works, we suggest that any anatomist or clinician who wishes to learn and teach about infant anatomy refer to Scammon's chapter before using any text or image from the Crelin books.

Risk factors for neonatal brachial plexus palsy attributed to anatomy, physiology, and evolution.

The inherent variable anatomy of the neonate and the uniquely-shaped maternal birth canal that is associated with the evolution of human bipedalism constitute risk factors for neonatal brachial plexus palsy (NBPP). For example, those neonates with a prefixed brachial plexus (BP) are at greater risk of trauma due to lateral neck traction during delivery than those with a normal or postfixed BP. Compared to adults, neonates also have extremely large and heavy heads (high head: body ratio) set upon necks with muscles and ligaments that are weak and poorly developed. Accordingly, insufficient cranial stability can place large torques on the cervical spinal nerves. In addition, the pelvic changes necessary for habitual bipedal posture resulted in a uniquely-shaped, obstruction-filled, sinusoidal birth canal, requiring the human fetus to complete a complicated series of rotations to successfully traverse it. Furthermore, although there are many risk factors that are known to contribute to NBPP, the specific anatomy and physiology of the neonate, except for macrosomia, is not considered to be one of them. In fact, currently, the amount of lateral traction applied to the neck during delivery is the overwhelming legal factor that is used to evaluate whether a birth attendant is liable in cases of permanent NBPP. Here, we suggest that the specific anatomy and physiology of the neonate and mother, which are clearly not within the control of the birth attendant, should also be considered when assessing liability in cases of NBPP.

Estrogen receptor beta expression and apoptosis of spermatocytes of mice overexpressing a rat androgen-binding protein transgene.

Progression of the first meiotic division in male germ cells is regulated by a variety of factors, including androgens and possibly estrogens. When this regulation fails, meiosis is arrested and primary spermatocytes degenerate by apoptosis. Earlier studies showed that overexpression of rat androgen-binding protein (ABP) in the testis of transgenic mice results in a partial meiotic arrest and apoptosis of pachytene spermatocytes. In view of the recent localization of estrogen receptor beta (ERbeta) in primary spermatocytes and data suggesting the ability of ERbeta to repress cellular proliferation, we tested the hypothesis that variations in the testicular steroid microenvironment caused by excess ABP produce changes in ERbeta expression in this cellular type that could be associated to the meiotic arrest and, eventually, to the induction of germ cell apoptosis observed in the ABP transgenic mice. Increased levels of ERbeta mRNA and protein were demonstrated in the testis of rat ABP transgenic mice compared with nontransgenic littermates by reverse transcriptase-polymerase chain reaction (RT-PCR) experiments, Northern blotting, and Western Blotting. The major differences were found when isolated germ cells of transgenic and nontransgenic littermates were analyzed by RT-PCR. In keeping with this finding, ERbeta was strongly immunolabeled in pachytene spermatocytes of rat ABP transgenic mice and localized in tubular stages in which TUNEL labeling was maximal. Confocal microscopy analysis of a fluorescent TUNEL assay and ERbeta immunohistochemistry revealed that degenerating pachytene spermatocytes overexpressed ERbeta. The present results are consistent with the interpretation that ERbeta is associated with the events that regulate negatively the progression of meiosis or that lead to spermatocyte apoptosis.

Increased expression of estrogen receptor beta in pachytene spermatocytes after short-term methoxyacetic acid administration.

Degeneration of primary spermatocytes by apoptosis occurs during normal spermatogenesis, as well as in several pathological conditions, including exposure to specific testicular toxicants. The mechanisms that regulate the death and survival of primary spermatocytes, however, are still not well understood. The recent localization of estrogen receptor beta (ERbeta) and P450 aromatase in pachytene spermatocytes suggests a role for estrogens in this step of spermatogenesis. Using a well-known model of pachytene spermatocyte apoptosis in adult rats consisting of the administration of methoxyacetic acid (MAA), we investigated the participation of ERbeta during the initial phase of apoptosis, prior to germ cell loss. Adult rats were treated with a single intraperitoneal dose of MAA, and DNA laddering analysis confirmed apoptotic cell death in the testis. In enriched germ cell fractions and testis from MAA-treated animals, ERbeta mRNA increased significantly at 3 and 6 hours, respectively. Next, stage-specific induction of ERbeta mRNA was demonstrated by use of laser capture microdissection of seminiferous tubules in combination with semiquantitative reverse transcription-polymerase chain reaction. The ERbeta protein also increased significantly after 6 hours and was mainly immunolocalized in the cytoplasm of pachytene spermatocytes of afflicted tubules. The cytoplasmic localization was confirmed by Western blot analysis of isolated cytoplasmic and nuclear fractions of testicular extracts. Finally, the MAA activation of ERbeta was tested in vitro in HepG2 cells cotransfected with ERbeta and a reporter construct that contained a consensus estrogen responsive element. Addition of MAA at similar doses used in vivo elicited a similar estrogenic activation as did estradiol at 1 nmol/L concentration. The present results raise the possibility that cytoplasmic ERbeta participates in the apoptotic process of pachytene spermatocytes induced by MAA. Whether MAA interacts with ERbeta in the cytoplasm of primary spermatocytes, preventing the progression of the first meiotic division, however, remains to be determined.

Methoxyacetic acid disregulation of androgen receptor and androgen-binding protein expression in adult rat testis.

Chemical agents can disrupt the balance between survival and apoptosis during spermatogenesis and thus give rise to reduced counts of spermatozoa (oligospermia). One such agent that produces significant germ cell apoptosis at specific stages of the cycle of the seminiferous epithelium is methoxy acetic acid (MAA), the active metabolite of a commonly used solvent, methoxyethanol. Although MAA gives rise to apoptosis of pachytene spermatocytes, it is not known whether MAA exerts a direct effect on germ cells or whether it also affects other testicular cell types such as the Sertoli cells. In the present investigation, we tested the hypothesis that MAA has direct effects on Sertoli cells in vivo. In MAA-treated rats, stage-specific expression of androgen receptor (AR) protein in Sertoli cells was significantly altered, as determined by AR immunohistochemistry. In MAA-treated animals, high AR expression was found in Sertoli cells coincident with the MAA-induced apoptosis of late-stage pachytene spermatocytes. The altered expression of AR in MAA-treated animals was also seen in seminiferous tubules harvested by laser capture microdissection. In addition to effects on AR expression, androgen-binding protein (ABP) mRNA levels were also altered in a stage-specific manner. Using a different system for mouse Sertoli cell lines TM4 and MSC-1, positive for either AR or ABP, respectively, we found a direct effect of MAA on ABP protein and mRNA expression in the MSC-1 cell but did not detect an effect on AR protein or mRNA expression in TM4 cells. Mouse fibroblasts that express endogenous AR were stably transfected with two AR promoter/reporter systems (MMTV-CAT and probasin-luciferase, respectively). We used these fibroblasts to examine the ability of MAA to potentiate dihydrotestosterone (DHT) activation of AR. Although MAA did not activate AR directly, it did potentiate DHT activation of the AR by 2- to 4-fold. MAA altered the expression level of AR and ABP in vivo and increased AR transcriptional activity in tissue culture cells. The abnormal spermatogenesis generated by MAA is at least partly due to direct effects on Sertoli cells. It is still unclear whether MAA elicits a proapoptotic signal from Sertoli cells or diminishes a prosurvival signal required by germ cells downstream to altering AR and ABP expression in a stage-specific fashion.