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Biomedical subjects

D A Costigan

Publications and source records attributed to D A Costigan.

7 recordsLinked to original sources
PubMed1995

Successful treatment of neuropathies in patients with diabetes mellitus.

OBJECTIVES: To report and characterize two forms of disabling progressive peripheral neuropathy in patients with diabetes mellitus, which respond to anti-inflammatory and/or anti-immune treatment. DESIGN: Review of clinical, electrophysiologic, and pathologic findings and results of treatment. SETTING: University medical center. PATIENTS: Twenty-one patients with diabetes mellitus to whom we gave anti-inflammatory and/or anti-immune treatment for progressive peripheral neuropathy during the past 6 years. MAIN OUTCOME MEASURES: Patients were interviewed and examined at intervals before and after beginning treatment with intravenous immunoglobulin (n = 15), prednisone (n = 13), cyclophosphamide (n = 5), plasma exchange (n = 3), and azathioprine (n = 1) (alone or in combination). RESULTS: Fifteen patients had evidence of axonal neuropathy by electrophysiologic studies (group A). All 15 patients had non-insulin-dependent diabetes mellitus, 10 patients had weight loss, and 13 patients had prominent involvement of thighs and/or thoracic bands consistent with diabetic amyotrophy or mononeuropathy multiplex. Small vessel disease was seen in all 10 patients who underwent biopsy, with perivascular or vascular inflammation seen in seven patients. Six patients had demyelinating neuropathy by electrophysiologic criteria (group B). All these patients had insulin-dependent diabetes mellitus, and no one had weight loss. The process was asymmetric in three patients and involved thoracic or abdominal regions in two patients. Onion bulbs were seen in all four patients who underwent biopsy, but no vascular inflammation or occlusion was seen. In all patients in both groups, worsening of their conditions stopped and improvement started after beginning treatment. CONCLUSION: Neuropathies responsive to anti-inflammatory and/or anti-immune therapy in patients with diabetes mellitus include (1) multifocal axonal neuropathy caused by inflammatory vasculopathy, predominantly in patients with non-insulin-dependent diabetes mellitus, indistinguishable from diabetic proximal neuropathy or mononeuropathy multiplex, and (2) demyelinating neuropathy indistinguishable from chronic inflammatory demyelinating polyneuropathy, predominantly in patients with insulin-dependent diabetes mellitus.

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PubMed1993

Genetic mapping of human heart-skeletal muscle adenine nucleotide translocator and its relationship to the facioscapulohumeral muscular dystrophy locus.

The mitochondrial heart-skeletal muscle adenine nucleotide translocator (ANT1) was regionally mapped to 4q35-qter using somatic cell hybrids containing deleted chromosome 4. The regional location was further refined through family studies using ANT1 intron and promoter nucleotide polymorphisms recognized by the restriction endonucleases MboII, NdeI, and HaeIII. Two alleles were found, each at a frequency of 0.5. The ANT1 locus was found to be closely linked to D4S139, D4S171, and the dominant skeletal muscle disease locus facioscapulohumeral muscular dystrophy (FSHD). A crossover that separated D4S171 and ANT1 from D4S139 was found. Since previous studies have established the chromosome 4 map order as centromere-D4S171-D4S139-FSHD, it was concluded that ANT1 is located on the side of D4S139, that is opposite from FSHD. This conclusion was confirmed by sequencing the exons and analyzing the transcripts of ANT1 from several FSHD patients and finding no evidence of aberration.

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PubMed1989

Spontaneous Kearns-Sayre/chronic external ophthalmoplegia plus syndrome associated with a mitochondrial DNA deletion: a slip-replication model and metabolic therapy.

The muscle mitochondria of a patient with Kearns-Sayre/chronic external ophthalmoplegia plus syndrome were found to be completely deficient in respiratory complex I activity and partially deficient in complex IV and V activities. Treatment of the patient with coenzyme Q10 and succinate resulted in clinical improvement of respiratory function, consistent with the respiratory deficiencies. Restriction enzyme analysis of the muscle mtDNA revealed a 4.9-kilobase deletion in 50% of the mtDNA molecules. Polymerase chain reaction analysis demonstrated that the deletion was present in the patient's muscle but not in her lymphocytes or platelets. Furthermore, the deletion was not present in the muscle or platelets of two sisters. Hence, the mutation probably occurred in the patient's somatic cells. Direct sequencing of polymerase chain reaction-amplified DNA revealed a 4977-base-pair deletion removing four genes for subunits of complex I, one gene for complex IV, two genes for complex V, and five genes for tRNAs, which paralleled the respiratory enzymes affected in the disease. A 13-base-pair direct repeat was observed upstream from both breakpoints. Relative to the direction of heavy-strand replication, the first repeat was retained and the second repeat was deleted, suggesting a slip-replication mechanism. Sequence analysis of the human mtDNA revealed many direct repeats of 10 base pairs or greater, indicating that this mechanism could account for other reported deletions. We postulate that the prevalence of direct repeats in the mtDNA is a consequence of the guanine-cytosine bias of the heavy and light strands.

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PubMed1985

Intramedullary spinal cord metastasis. A clinicopathological study of 13 cases.

A retrospective autopsy study of 627 patients with systemic cancer disclosed 153 patients with metastasis to the central nervous system (CNS) and 13 patients with intramedullary spinal cord metastasis (ISM). Thus, the frequency of ISM was 8.5% of cases of metastasis to the CNS and 2.1% of all cases of cancer. Bronchogenic carcinoma accounted for 11 cases of ISM, and breast carcinoma and melanoma for the other two. There were two distinct patterns of spinal cord involvement, indicating spread of tumor to the cord by two different routes. In nine of the 13 ISM patients a metastasis was found deep within the spinal cord, unassociated with leptomeningeal carcinomatosis; this most likely resulted from hematogenous spread of tumor from a pulmonary source. In the other four patients there was focal or multifocal direct extension of leptomeningeal metastatic tumor across the pia into the parenchyma of the cord. Only four of the 13 patients had a clinical myelopathy; in three of these four this was the presenting feature of an occult lung cancer.

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