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Biomedical subjects

R A Kyle

Publications and source records attributed to R A Kyle.

At least 19 recordsLinked to original sources
PubMed1992

Familial amyloidosis: a study of 52 North American-born patients examined during a 30-year period.

Between 1961 and 1990, 52 patients with biopsy-proven familial amyloidosis born in North America were examined at the Mayo Clinic. At the time of diagnosis of familial amyloidosis, 83% of these patients had peripheral neuropathy, 33% had autonomic neuropathy, and 27% had cardiomyopathy. Renal disease was noted in fewer than 10%, and liver involvement was rare. The median age at diagnosis was 64 years. The sensitivity of various diagnostic biopsies was similar to that for primary amyloidosis: deposits of amyloid were found in 77 and 78% of the subcutaneous fat aspirates or rectal biopsy specimens, respectively, and in 41% of specimens of bone marrow. The median duration of survival of 5.8 years for patients with inherited amyloidosis was superior to that for patients with primary amyloidosis. When patients were stratified by organ involvement, the survival of patients with familial amyloidosis remained superior. The presence of cardiomyopathy and an interactive variable of age and the presence of autonomic neuropathy were powerful predictors of survival. Of the 52 patients, 22 died, 12 (55%) of cardiac failure or cardiac arrhythmia. Nine patients (41%) died of inanition in conjunction with progressive peripheral or autonomic neuropathy. Transthyretin was identified by immunohistochemical studies in 31 of the 34 tissue specimens tested. A transthyretin mutation was identified in 24 of the 31. A transthyretin mutation was found in five additional patients for whom tissue was unavailable for immunostaining.

Adult↗
PubMed1992

Amyloid localized to tenosynovium at carpal tunnel release. Immunohistochemical identification of amyloid type.

Thirty-five patients seen at the Mayo Clinic from 1968 to 1977 who had carpal tunnel syndrome and local deposition of amyloid without evidence of systemic amyloidosis were identified. The unlabeled immunoperoxidase method was used with antisera against purified amyloid proteins of the AA, A kappa, A lambda, AF/ASC1 (prealbumin) (transthyretin), and AB (beta 2-microglobulin) types. In 33 of the 35 patients, amyloid stained with antisera to transthyretin; in the remaining 2 patients, the amyloid did not stain with any antisera. Nine of the 35 patients had a monoclonal protein in the serum, and 2 had a monoclonal light chain in the urine. Systemic amyloidosis or multiple myeloma did not develop in any of these 11 patients. During follow-up, systemic amyloidosis developed in only 2 of the 35 patients: 1 had senile systemic amyloidosis and 1 had tissue that was inadequate for immunohistochemical staining. Amyloid localized to the tenosynovium consists of transthyretin, and systemic amyloidosis rarely develops.

Aged↗
PubMed1992

Immunohistochemical characterization of amyloid proteins in sural nerves and clinical associations in amyloid neuropathy.

To test whether immunohistochemical characterization of proteins in amyloid deposits in biopsied sural nerves gives reliable and useful diagnostic information using commercially available reagents, biopsy specimens of sural nerves from 38 patients with amyloid neuropathy were studied. Transthyretin (TTR) was detected in the amyloid deposits of 11 nerves, lambda light chains (LC) in 8 nerves, kappa LC in 7 nerves, and both lambda and kappa LC in 3 nerves. In 9 nerves, the amyloid deposits were too small to allow adequate immunohistochemical characterization of amyloid proteins in serial sections. Evidence that immunohistochemical characterization was correct came from: 1) evaluation of kin, 2) search for monoclonal proteins in the plasma, and 3) sequencing of the gene abnormalities in TTR+ cases. In 9 of 11 TTR+ cases, in which DNA could be obtained, sequencing of the gene showed that each of the 9 cases was heterozygous for a gene mutation; 7 had previously described mutations and 2 undescribed mutations. Therefore, in the nine sporadic cases without plasma monoclonal light chains, the immunohistochemical characterization correctly identified the protein in amyloid as transthyretin. Likewise, there was a high concordance between immunoglobulin light chains in plasma and light chains in amyloid in primary amyloidosis. Evaluation of the type, distribution, and severity of the neurologic symptoms and deficits showed: 1) the sensorimotor and autonomic neuropathy of amyloidosis characteristically affects proximal as well as distal limbs, and 2) the type of amyloidosis probably cannot be determined from the characteristics or severity of the neuropathy alone or from the location or size of amyloid deposits in nerve.

Aged↗
PubMed1992

Monoclonal proteins in neuropathy.

The presence of a monoclonal protein in the serum of a patient with peripheral neuropathy raises the suspicion of systemic amyloidosis, POEMS syndrome, macroglobulinemia, multiple myeloma, or lymphoma. If these conditions are excluded, the patient is classified as having a monoclonal gammopathy of undetermined significance (MGUS) with an associated neuropathy. Approximately one half of patients with peripheral neuropathy and IgM monoclonal gammopathy have IgM antibodies that bind to a myelin-associated glycoprotein (MAG). In addition to MAG, other antigens such as glycolipids or gangliosides represent other target antigens. Monoclonal gammopathies and motor neuron diseases have also been reported. Sensorimotor peripheral neuropathy occurs in about 15% of patients with primary amyloidosis but is uncommon in multiple myeloma.

Autoantibodies↗
PubMed1992

Dialysis support of patients with primary systemic amyloidosis. A study of 211 patients.

BACKGROUND: The study assessed dialysis support in patients with primary systemic amyloidosis without associated multiple myeloma in whom renal insufficiency developed. METHODS: The study group consisted of 211 patients with biopsy-proved primary systemic amyloidosis examined at the Mayo Clinic, Rochester, Minn. No patient was lost to follow-up. RESULTS: Thirty-seven (18%) of the patients received dialysis therapy. Of those presenting with renal amyloid, one third received dialysis. The median time from diagnosis to initiation of dialysis was 13.8 months. The median survival for patients from the start of dialysis was 8.2 months. There was no survival difference between hemodialysis (n = 27) and peritoneal dialysis (n = 10). The most important predictors of which patients would ultimately require dialysis were the 24-hour urinary protein loss and serum creatinine values at the time amyloidosis was diagnosed. None of the patients seen at diagnosis with a normal serum creatinine value and proteinuria of less than 2 g/d required dialysis during follow-up. Of the 37 patients who received dialysis, 31 died, and 21 of the 31 died as a result of extrarenal progression of their systemic amyloidosis. Fifteen of the 31 deaths were a result of cardiac amyloidosis. All long-term survivors had normal echocardiograms without evidence of amyloid. CONCLUSION: Eighteen percent of patients with primary amyloidosis undergo dialysis. The 24-hour urinary protein loss and creatinine values are helpful in predicting which patients eventually will require dialysis. The median survival for patients starting dialysis is less than 1 year. Patients whose two-dimensional echocardiograms are normal are most likely to derive long-term benefit from dialysis.

Aged↗