Tuesday, March 5, 2013

Article Reviews - The 1980s

My previous article review actually covered three articles from the 1970s which provided some history of hereditary renal amyloidosis, before the fibrinogen mutation was discovered. This post will cover three more articles, this time from the 1980s. I don't actually have any of these articles, but based on their abstracts and what is said about them in other articles I do have, they seem to have some historical significance.

(Before getting into the articles, I'll note that since this is the first post of the month, the always exciting section on the monthly blog stats will be at the end of this post.)

Since I don't have any of these three articles I'll just give same basic info about each one and then discuss them as a whole.

[Update: The following article was reviewed again on 9-6-13.]

Authors: Mornaghi, Rubinstein, and Franklin

Journal: Transactions of the Association of American Physicians (1981)

I have not found an abstract for this article online, but based on what has been written about it when referred to in other articles I know it is a report on three Irish-American siblings with a clinical history of nephropathy at the ages of 49, 52 and 55.

[Update: The following article was reviewed again on 9-18-13.]

Authors: Lanham, Meltzer, De Beer, Hughes and Pepys (yes, that Pepys)

Journal: QJM: An International Journal of Medicine (1982)

A 23 year old Englishman presented with keratoconjunctivitis sicca and was found to have systemic amyloidosis. Five members of his family in two generations also had non-neuropathic amyloid particularly affecting the kidneys. This conforms to the Ostertag type of hereditary amyloidosis. Amyloid deposits in the proband showed permanganate-sensitive Congophilia and positive immunofluorescence staining for P component, but were negative for amyloid A and prealbumin. These observations suggested that the fibril protein in this patient was immunochemically distinct from the amyloid fibrils characterized hitherto.

[Update: The following article was reviewed again on 9-6-13.]

Title: Familial renal amyloidosis: Case reports and genetic studies (3)

Authors: Mornaghi, Rubinstein, and Franklin

Journal: The American Journal of Medicine (October 1982)

Rapidly progressive biopsy-proved renal amyloidosis developed in three brothers, aged 49, 52, and 55, of Irish-American origin. None had evidence of a plasma cell dyscrasia, a monoclonal serum or urine protein, or any underlying chronic disease. Immunoperoxidase staining of one pulmonary and one renal biopsy specimen was negative for Amyloid A (AA), Amyloid L (AL), and prealbumin. To investigate factors that might play a role in the disease, the subjects and 21 relatives were typed for antigens of the A, B, C, and DR loci and the linked marker genes for factor B and glyoxalase. The ability of macrophages to degrade serum amyloid A (SAA) [1] was examined. One brother yielded an intermediate AA-like produce similar to what is seen in most patients with AA or AL amyloidosis and 40 percent of normal subjects. The other two degraded SAA completely to small peptides. Analysis of the families revealed first that the disease was not linked to the major histocompatibility complex. We were unable to demonstrate a genetic relationship between processing of SAA by peripheral mononuclear cells and the human leukocyte antigen locus. Finally, the pattern of SAA degradation was not associated with the development of the disease.

The two articles authored by Mornaghi are reporting on the same family (Irish-American siblings), so these articles from the 1980s report on two more families with a hereditary form of amyloidosis that primarily affects the kidneys. Most of the medical terminology in the abstracts is beyond my understanding, but here are some key points I picked up:

  • The abstract of the Lanham article indicates they determined the amyloid fibrils themselves are different than amyloid fibrils previously analyzed. I assume the previously analyzed fibrils were from patients with the most common form of amyloidosis, known as primary or AL amyloidosis.
  • The Mornaghi report indicates they also determined these patients did not have other types of amyloidosis that were known at the time, specifically AL and AA amyloidosis. This report also appears to describe a significant effort to determine the genetics behind this form of amyloidosis by doing various types of analysis on 21 relatives of these three siblings.

So that was the state of things in the early 1980s. A few isolated families in the US and England have been determined to have a hereditary form of amyloidosis that affects the kidneys, and the amyloid fibrils (the "stuff" the damages the kidneys) appear to be different than the fibrils associated with other more common types of amyloidosis. The symptoms and progression of the disease are being documented, as are the detailed pathological findings of analyzed tissue samples.

In really simple terms, the medical community at this point knows "what" is going on but they don't know "why." The cause is likely genetic, but they are a long way from determining the specific genetic cause (or causes). We'll need a few more years for the knowledge of genetics and the available technology to advance so medical researchers can zero in on the genetic cause. In fact, the next article I'll be reviewing is "Inherited Amyloidosis" from 1991.

=====Monthly Blog Status Update
Months behind as of February 2013: 2
Months behind as of March 2013: zero!

The "Months Behind" blog stat can officially be retired now that I have caught up to the present day. I'm not sure what to replace it with, so for now I'll go with something easy, which is pageviews.

Total posts: 64 (8 in February)

Total pageviews: 1016 (~120 in February)

Email subscribers: 4 (Don't worry. I can't see the email addresses used to subscribe, only the count.)

Number of countries that have viewed the blog: 26

New countries that viewed the blog in February:

New Zealand

Citations for the articles discussed in this post:

(1) Mornaghi, R., P. Rubinstein, and E. C. Franklin. 1981. Studies on the pathogenesis of a familial form of renal amyloidosis. Trans. Assoc. Am. Phys. 94:21 1-216.

(2) Lanham, J. G., M. L. Meltzer, F. C. De Beer, G. R. V. Hughes, and M. B. Pepys. 1982. Familial amyloidosis of Ostertag. Q. J. Med. 201:25-32.

(3) Mornaghi, R., P. Rubinstein, and E. C. Franklin. 1982. Familial renal amyloidosis: case reports and genetic studies. Am. J. Med. 73:609-614.

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