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Biomedical subjects

K D Brandt

Publications and source records attributed to K D Brandt.

At least 19 recordsLinked to original sources

Effect of calcipenia on proteoglycan metabolism and aggregation in normal articular cartilage in vitro.

Glycosaminoglycan synthesis in normal adult dog knee cartilage cultured in medium containing 0, 0.3 MM- and 0.9 mM-Ca2+ was 52, 67 and 78%, respectively, of that in cartilage from the same joints cultured in a normal concentration of Ca2+, i.e. 1.8 mM. Pulse-chase experiments indicated that the rate of degradiation of glycosaminoglycans in cartilage cultured in the absence of Ca2+ was similar to that of glycosaminoglycans in cartilage cultured in 1.8 mM-Ca2+. Although [35S]sulphate incorporation into glycosaminoglycans was decreased in the presence of calcipenia, [3H]leucine incorporation into protein was unaffected. The average hydrodynamic size of newly synthesized proteoglycan aggregates and purified disaggregated proteoglycans from cartilage cultured in the absence of Ca2+ was similar to that of aggregates and disaggregated proteoglycans from cartilage cultured in 1.8 mM-Ca2+.

Animals

Systemic lupus erythematosus: association with psoralen--ultraviolet-A treatment of psoriasis.

Systemic lupus erythematosus (SLE) developed in as 23-year-old woman with psoriasis during treatment with psoralen-ultraviolet-A (PUVA). The connective tissue disease was characterized by an erythematous rash, hair loss, nephritis, splenomegaly, seizures, and coma. Serum antinuclear antibodies were present in high titer, and hypocomplementemia developed. Antibodies to native or ultraviolet-irradiated DNA were not demonstrated. While the association of psoriasis and lupus may have been fortuitous, the temporal relationships suggest that PUVA treatment in this case may have been of pathogenetic importance in the development of the connective tissue disease.

Adult

Joint effusions after kidney transplantation.

Thirty-seven consecutive renal transplant recipients were studied prospectively for joint disease. Six developed arthralgias while corticosteroid doses were being lowered. Eleven patients (30%) developed knee effusions at a mean interval of 10 days following transplantation. Synovial fluids were colorless or very pale yellow, with few leukocytes (mean, 28/mm3). These benign transudative effusions did not correlate with immunologic abnormalities, transplant rejection, crystal deposition, or avascular necrosis and may have been due to high dose oral corticosteroid therapy.

Adolescent

Development and reversal of a proteoglycan aggregation defect in normal canine knee cartilage after immobilization.

Healthy adult dogs were studied for a defect in proteoglycan aggregation by immobilizing one limb for varying periods of time. Immobilization for 6 days resulted in a 41% reduction in proteoglycan synthesis by articular cartilage from the restrained knee compared with the contralateral control knee. After 3 weeks of immobilization, proteoglycan aggregation was no longer demonstrable in cartilage from the constrained limb. The aggregation defect was rapidly reversible and aggregates were again normal size 2 weeks after removal of a cast that had been worn for 6 weeks.

Animals

Effect of salicylate on proteoglycan metabolism in normal canine articular cartilage in vitro.

In osteoarthritis, diminished aggregation of articular cartilage proteoglycans affects tissue biomechanics. Since salicylates are commonly employed in treatment of osteoarthritis, we examined the effect of sodium salicylate on proteoglycan metabolism and aggregation in normal canine articular cartilage. At salicylate concentrations of 10(-3)M, 5 X 10(-3)M and 10(-2)M, net proteoglycan synthesis in normal canine articular cartilage was 73%, 42% and 16% respectively, of control levels. Catabolism of glycosaminoglycans in the presence of 10(-3)M salicylate (which corresponds to a serum salicylate level of 20-25 mg %) was the same as that in control cartilage, while higher concentrations of the drug increased the rate of degradation. The hydrodynamic size of newly synthesized proteoglycan aggregates and of disaggregated proteoglycans was unaffected by sodium salicylate.

Animals

Enhancement of urate solubility by connective tissue. II. Inhibition of sodium urate crystallisation by cation exchange.

The urate concentration of the supernatant was greater after supersaturated solutions of sodium urate were incubated in a suspension of CM-Sephadex C-25 than in one of Sephadex G-25. The supernatant urate concentration was greater when the CM-Sephadex had been equilibrated with potassium than with sodium. The results are analogous with those obtained in studies of urate solubility in proteoglycan solutions. They are consistent with the Donnan effect and the hypothesis that the glycosaminoglycans within the proteoglycan molecule function as cation exchangers which, when charged with potassium, exchange with the sodium of the urate molecule, leading to formation of highly soluble potassium urate.

Cation Exchange Resins

Popliteal cyst mimicking thrombophlebitis as the first indication of knee disease.

Five patients, none of whom were previously known to have knee disease, developed leg swelling which was misdiagnosed as thrombophlebitis. Four were treated with anticoagulants and one developed a large calf hematoma requiring fasciotomy. The primary physicians failed to appreciate evidence of knee disease in these patients, although the rheumatology consultant found knee effusion, and a popliteal cyst was found by arthrography or ultrasonography in every case. The occurrence of popliteal cyst as the first sign of knee disease emphasizes the importance of careful examination of the knee in all patients with a clinical picture of thrombophlebitis.

Adult

Enhancement of urate solubility by connective tissue. I. Effect of proteoglycan aggregates and buffer cation.

Proteoglycan aggregates (PGC) facilitated dissolution of 2 1/2 times more sodium urate crystals than nonaggregated proteoglycans. This effect of aggregates on urate solubility was abolished by digestion of the aggregates with hyaluronic acid beta1 leads to 3 hydrolase. PGC, however, did not sustain urate concentrations in supersaturated solutions. Potassium urate was severalfold more soluble than sodium urate. In vivo, where they exist predominantly as their sodium salts in the extracellular connective tissue, proteoglycans may not markedly influence the solubility of sodium urate.

Animals

Degradative enzymes of cartilage. Effects of freeze-thawing of the tissue prior to extraction, and of protease inhibitors, on proteoglycans extracted with iso-osmotic neutral salt and 4 M guanidinium chloride.

The effects of freeze-thawing of the tissue, and of protease inhibitors, on proteoglycans extracted sequentially from pig laryngeal cartilage with 0.15 M sodium acetate and 4 M guanidinium chloride were examined. Freeze-thawing of the tissue prior to extraction resulted in an increase in the proportion of smaller-sized proteoglycans in the sodium acetate extracts and a decrease in the proportion of aggregated proteoglycans in 4 M guanidinium extracts. In addition, a slight decrease in the hydrodynamic size of purified disaggregated proteoglycans was noted after freeze-thawing of the cartilage. When the protease inhibitors EDTA, 6-aminohexanoic acid and benzamidine hydrochloride were added to the sodium acetate buffer the yields of proteoglycans from fresh and freeze-thawed cartilage were diminished, but the inhibitors had no effect on the hydrodynamic size of the proteoglycans extracted with sodium acetate. Addition of the protease inhibitors to the 4 M guanidinium solvent increased the proportion of proteoglycans present in aggregates. The highest proportion of aggregated proteoglycans was obtained when fresh tissue was extracted in the presence of the inhibitors.

Acetates

Fibrous replacement of the deltoid muscle: a remediable cause of abduction contracture of the shoulder in scleroderma.

A 32-year-old male with progressive systemic sclerosis developed shoulder abduction contractures secondary to fibrous replacement of the central portions of his deltoid muscles. Surgical release of the fibrous bands resulted in prompt restoration of nearly full shoulder motion. One month later, however, a similar band developed in the triceps muscle. Although the association in this cases may have been coincidental, the neraly simultaneous onset of muscle fibrosis and cutaneous manifestations of progressive systemic sclerosis suggests a causal relationship.

Adult

Herniation of mitral leaflets in the Ehlers-Danlos syndrome.

A 47 year old patient with the Ehlers-Danlos syndrome (hypermobility of the joints, hyperextensibility of the skin and atrophic cutaneous scars) was evaluated because of a mitral regurgitant murmur and paroxysmal atrial tachycardia. Angiocardiography and echocardiography demonstrated marked systolic herniation of the posterior leaflets of the mitral valve. An echocardiogram from the patient's daughter, who also had paroxysmal atrial tachycardia, revealed the same abnormality. Although a "floppy" valve is common in Marfan's syndrome, this report emphasizes that it may also occur in patients with other heritable disorders of connective tissue.

Cineangiography

Neuropathy, M components, and amyloid.

Of eighty-seven patients with nonhereditary systemic amyloidosis, ten had evidence of peripheral neuropathy. There was median-nerve neuropathy due to infiltration of the flexor retinaculum with amyloid in six patients. Two patients had diffuse sensorimotor neuropathy and two patients had sensory loss without evidence of motor impairment--three of these cases had amyloid deposition demonstrated by nerve biopsy. Neurological manifestations in all ten patients preceded other evidence of amyloidosis by 6 months-4 years (mean, 1 to 5 years). Neuropathy occurred in six of thirty-eight patients with primary amyloidosis and four of fourteen with amyloidosis associated with malignant B-cell dyscraias; and all patients with neuropathy had either a serum-M-component or Bence-Jones proteinuria. In contrast, neuropathy was not noted in any of the fifty-six patients in this series who had no evidence of a monoclonal gammopathy (thirty-five with secondary and twenty-one with primary amyloidosis).

Amyloidosis

Stimulation of glycosaminoglycan biosynthesis by amyloid fibrils.

Since amyloid-laden organs have an increased glycosaminoglycan content, the effect of amyloid fibrils on glycosaminoglycan metabolism by normal fibroblasts was examined. In comparison with controls, synthesis of glycosaminoglycans, primarily hyaluronic acid, was increased by an average of 48 and 93% respectively when 0.1 and 1.0 mg of amyloid fibrils/ml was added to the cultures.

Amyloid

Cerebral disorders of vision in systemic lupus erythematosus.

Sensory neuroophthalmic abnormalities due to cerebral lupus erythematosus, with involvement of visual pathways posterior to the optic chiasm, occurred in 12 patients with systemic lupus erhthematosus. Five underwent detailed evaluation because of an hallucination, 4 for visual loss, and 3 for both. Hallucinations were either unformed (for example, bright lights, straight lines) or highly formed (for example, faces), in which case they were invariably recognized by the patient as inappropriate. In no instance did they occur in association with delirium, confusion, or use of hallucinogenic drugs. Patients with loss of vision had scotomas, homonymous field defects, and cortical blindness. These features indicate disease in the posterior cerebral artery circulation, a localization often supported by ancillary neurologic findings, for example, vocal cord paralysis, diminished gag reflex. Thus, various visual dysfunctions may occur in systemic lupus erythematosus due to cerebral vasculitis. At times they may be the most prominent and disabling feature of the disorder.

Adrenal Cortex Hormones

Cardiovascular abnormalities in the Marfanoid hypermobility syndrome.

Two patients are described who had the body habitus of the Marfan syndrome, cutaneous hyperextensibility, and atrophic "cigarette paper" scars. One had mild joint hypermobility and the other had generalized ligamentous laxity. Both individuals are considered to be examples of the Marfanoid hypermobility syndrome, a generalized heritable connective tissue disease with features of, but genetically distinct from, the Marfan and Ehlers-Danlos syndromes. One patient had a "floppy" mitral valve and the other had an aortic aneurysm due to cystic medionecrosis of the aorta; both findings provide evidence that cardiovascular disease may be a significant feature of this syndrome.

Adult

Treatment of septic arthritis: comparison of needle aspiration and surgery as initial modes of joint drainage.

Surgery and needle aspiraton have been evaluated as initial modes of drainage in 59 patients with acute septic arthritis. Full recovery was noted in 42% treated surgically at the outset. On the other hand, 67% of those treated by needle aspiration recovered without sequelae, despite the greater prevalence in this group of adverse host factor-eg, serious underlying illness, concommitant extraarticular infection, prior arthritis in the infected joint, and recent antibiotic or immunosuppressive therapy.

Acute Disease