Biography of J. Isfred Isidore Hofbauer (J. Hofbauer)

J. Isfred Isidore Hofbauer Portrait
undated photo of J. Hofbauer [1]

J. (Jsidro) Isfred Isidore Hofbauer or simply J. Hofbauer (born September 8th, 1871 in Vienna, Austria - March 13th, 1961 in Cincinnati, US) was a Austrian-born American gynecologist who performed extensive studies of obstetric organ systems and pioneered new treatments with regard to childbirth. Furthermore, he doubled as an oncologist formulating early operations to treat breast cancer. [2]

Early Life

Hofbauer was of Scandinavian and Austrian heritage. [3] His parents were Moritz Hofbauer and Jeanette Gewitsch. [4]

John's Hopkins Medical School Women's Clinic - circa 1924
Johns Hopkins Hospital Women's Clinic circa 1924. [5]

University Associations

He studied at medicine at the University of Vienna. He did his residency at the Nothnagel Clinic and the Women's Clinic at the Bettina Pavilion. He studied under Friedrich Shauta and Ernst Wertheim for his postgraduate work. He was the lead doctor in the Women's Clinic at Königsberg University from between 1906 and 1912. In 1909 he became the chair of gynecology and obstetrics at the University of Königsberg. He was invited in 1924 by John Whitridge Williams to join the faculty of Johns Hopkins University, where he served as an Associate Professor. In 1933 he moved to the University of Cincinnati where he continued to be an Associate Professor of Obstetrics and gynecologist at the Jewish and Good Samaritan Hospitals. [2,3,4]

Scientific Career

In 1896, J. Hofbauer proposed a "neuclein" treatment for severe infections about childbirth, providing a positive assessment as to its potential due to positive results in seven patients. [6] He continued to experiment with this treatment, continuing to report positive while others in the field attempted to extend the field to inoculation from disease as well. [7] Hofbauer was known to emphasize the techniques efficiency when delivered via the stomach. [7] At the time the "neuclein" was defined to be the part of blood serum left over after digestion within the stomach. [8] Although it was theorized that special "white blood cells" within the blood with phagocytic properties were responsible for the remedy for bacterial infection, this was only one of a few competing theories. [8] The injection of serum was typically accompanied by a saline solution injection and occasionally damaged the bone marrow of the patients [9]. Studies by other researchers to "inoculate" for specific bacteria with blood serum injections were unsuccessful [7].

J. Hofbauer - Biology of the Human Placenta Cover Page
Translation: Biology of the Human Placenta with a special emphasis on the question of fetal nourishment by Dr. J. Hofbauer

J. Hofbauer published a book in 1905 regarding a morphological study he conducted of the human placenta. [10] He described visible "fat cells" within the developing fetus. [11] There was also a special kind of "vacuolated" cell that he described in great detail within the book.

"Vacuolated" cells within the first Table in Appendix of J. Hofbauer's book.

In his 1925 paper entitled "THE FUNCTION OF THE HOFBAUER CELLS OF THE CHORIONIC VILLUS PARTICULARLY IN RELATION TO ACUTE INFECTION AND SYPHILIS" [12], J. Hofbauer translated his original description of the cells which would later become known as Hofbauer cells:
“These specific cells make their appearance by the end of the fourth week of pregnancy. They are comparatively abundant in the early stages of the placenta and decrease in number later on, as the connective tissue of the villus gradually assumes a more fibrous character. The duration of life of the individual cells is shown by the fact that they vanish after total vacuolization. In the cytoplasm which primarily contains homogenous or delicate granules, minute pellucid spots gradually appear about the periphery of the nucleus; later increase in size, and form a clear area surrounding it. These spaces which are filled with fluid and are separated from one another by thin septa, may fuse together, and thus give rise to larger vacuoles. Similar foam-like structures subsequently occur in the peripheral zone of the cells, as well. Furthermore, an essential part of the cytoplasm is represented by smaller and larger granules. In the beginning, these cells are intimately connected with the stroma cells of the villi and are to be considered as descendants of the original mesenchyme. Marchand holds the same view. Staining fresh placental tissue with neutral red throws the vacuolated cells into the boldest relief, while the surrounding tissue remains unstained. It is the granules and the vacuoles of the cells which take up the dye with avidity. These are the fundamental structural constituents of the cells in question, and they may play a considerable biologic part. As to their physiologic role, we can only say that they probably possess a digestive function,--a view which is supported by the presence of fat in the vacuoles, as well as of neutral red. The phagocytic power is further supported by the fact that at the stage of development, when the nucleated red blood cells lose their nuclei, I could demonstrate the disintegration of their nuclei within the fetal capillaries of the chorionic villi, and that the fragments of the nuclei were engulfed by the cytoplasm of a type of cells quite comparable in structure to our vacuolated cells. As this phenomenon could be observed distinctly in various specimens, it became obvious that our cells may bc regarded as wandering cells, which had gained access to the fetal blood stream, and thereby constituted a portion of its white cells.” 
He also included a clearer figure with stained Hofbauer cells (HBCs) exclusively within his 1925 paper, which then goes on the delineate rapid increase in the number of HBCs in response acute infection. These kinds of morphological studies were common within Hofbauer's research. This indicates that the Hofbauer cells were being seriously considered to be macrophages as early as 1924/1925. [12]

Hofbauer Cells - 1925
Fig. 1: Section through normal villus at third month, showing Hofbauer cells.

Hofbauer also found that these cells reacted in a similar manner to a certain dye as other cells within the bone marrow and Kupffer cells, foreshadowing their future similarities as tissue-resident macrophages. [12]

Advertisement for Pituitary Extract featuring a glowing review by Hofbauer. [13] 

He was also one of the first gynecologists to utilize pituitrin, an extraction from cattle pituitary hormones, in order to help deal with labor pains. By the time the advertisement above was published, Hofbauer had applied the treatment to twelve patients and stated that "there were no unfavorable after-effects." [13] He recommended the product for "all forms of primary and secondary uterine inertia," noting that the introduction of these hormones has removed the need for many once common complex surgical procedures. [14] Reflecting in 1955 within his paper, Forty Years of Postpituitary Extract in Obstetrics, Hofbauer wrote the following [15]:
THE importance of the initial impulse that a fascinating experimental observation may inspire for its application to spheres of considerable practical interest is forcefully illustrated by the mosaic of significant advances which resulted from the report by H. H. Dale of vigorous contractions of the virgin guinea pig's uterus suspended in a neutral solution, induced by the addition of post-pituitary extract. Factual background data form the basis of the present attempt of an objective evaluation of the merits of post-pituitary preparations as a therapeutic standby, while an exhaustive review of the subject is not in the scope of this survey. 
The reflection above characters much of Hofbauer's research: a kind of try-and-see approach that attempted to find success and justified the original experiments with factual evidence afterwards.

Hofbauer also attempted to connect the human pituitary gland to the origins of cancer within mothers. He saw the cancer as a continued production of growth hormone that led to increased cell division. Although he was unable to link his theory to all cancers, Hofbauer successfully utilized X-ray radiology on the pituitary to help patients which was a precursor to modern radiation treatments. [16]

Character

Thomas F. Baskett wrote in his book, Eponyms and Names in Obstetrics and Gynaecology, that Hofbauer was "arrogant, egotistical and aggressive." Baskett recalls a story where Hofbauer told a junior colleague to write about their meeting in this manner: "Go home and write in your diary that today you talked to Hofbauer." [3]

Supplemental Image

Stained Placental Cross-Section by Hofbauer
Stained Placental Cross-Section by Hofbauer for Iron Absorption (1905)

References

1.
J. Isfred Isidor Hofbauer, http://hdl.handle.net/2193/5138JF11M.
2.
Times S to TNY. Dr. Isfred Hofbauer, a Gynecologist, 89. New York Times. 1961:39.
3.
Baskett TF. Eponyms and Names in Obstetrics and Gynaecology. 3rd ed. Cambridge University Press; 2019. doi:10.1017/9781108421706
4.
Österreichische Nationalbibliothek, ed. Handbuch Österreichischer Autorinnen Und Autoren Jüdischer Herkunft: 18. Bis 20. Jahrhundert. DE GRUYTER SAUR; 2002. doi:10.1515/9783110949001
5.
[Johns Hopkins Hospital Woman’s Clinic, circa 1924]. Flickr. Accessed May 28, 2020. https://www.flickr.com/photos/medical_archives/3570325755/
6.
Company P Davis &. Nuclein Therapy. Parke, Davis & Company; 1900.
7.
The Cincinnati Lancet-Clinic. J.C. Culbertson; 1904.
8.
Ames D. THE NATURE OF THE LEUCOCYTOSIS PRODUCED BY NUCLEINIC ACID; A PRELIMINARY EXPERIMENTAL STUDY. JAMA. 1897;XXIX(10):472. doi:10.1001/jama.1897.02440360016002e
9.
The American Journal of Obstetrics and Diseases of Women and Children. W.A. Townsend & Adams; 1903.
10.
Hofbauer Jsidro. Grundzüge Einer Biologie Der Menschlichen Plazenta, Mit Besonderer Berucksichtigung Fragen Der Fötalen Ernährung. W. Braumüller; 1905. Accessed May 28, 2020. https://catalog.hathitrust.org/Record/006744605
11.
Archives of Internal Medicine. American Medical Association.; 1923.
12.
Hofbauer J. The function of the hofbauer cells of the chorionic villus particularly in relation to acute infection and syphilis. American Journal of Obstetrics and Gynecology. 1925;10(1):1-14. doi:10.1016/S0002-9378(25)90514-5
13.
The Journal of the Arkansas Medical Society. Arkansas Medical Society.; 1912.
14.
Therapeutic Notes. Parke, Davis & Company; 1912.
15.
Hofbauer J. Forty Years of Postpituitary Extract in Obstetrics. American Journal of Obstetrics and Gynecology. 1955;69(4):822-825. doi:10.1016/S0002-9378(16)38084-X

16.
TIMES WLLS to TNY. GLAND INFLUENCE TRACED IN CANCER: Cell Growth Is Linked With Pituitary Overfunction in Cases of Mothers. CHECK BY X-RAY REPORTED Medical Association is Also Told of Many Infections Laid to Sinus Trouble. New York Times. 1934:16.

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