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Biomedical subjects

R M Bennett

Publications and source records attributed to R M Bennett.

At least 127 records · Page 7Linked to original sources

The arthritis of mixed connective tissue disease.

Twenty patients with mixed connective tissue disease were followed for 5 years. Arthritis occurred in all 20 patients, being the presenting complaint in 11 patients. The joints most frequently involved were the proximal interphalangeal (PIP), metacarpophalangeal (MCP), wrists, metatarsophalangeal (MTP), and knee; the distribution tended to be symmetrical, mimicking early rheumatoid arthritis. Joint deformities occurred in 6 patients, but apart from 1 patient with arthritis mutilans, significant functional impairment was not encountered. Radiologically small punched out bone erosions, asymmetrically distributed, were the most characteristic finding; other notable changes were aseptic necrosis, tuft erosions, and periarticular calcification. Joint effusions were non-inflammatory, the cellular content was predominantly lymphocytic and the C3 level was normal. Most cases were controlled with non-steroidal anti-inflammatory agents and invariably responded to prednisone less than or equal to 7.5 mg/day.

Adolescent↗

Immune complex nephropathy in mixed connective tissue disease.

Initial reports on the clinical spectrum of mixed connective tissue disease (MCTD) indicated that renal involvement was uncommon. Four of 20 patients with MCTD underwent renal biopsy and all showed evidence of immune complex trapping with a membranous glomerulonephritis in three patients. Clinically evident renal disease was absent in two patients. These findings suggest that renal involvement in MCTD may be more prevalent than previously indicated.

Adolescent↗

Eosinophilic fasciitis. Case report and review of the literature.

Eosinophilic fasciitis is a recently described rheumatic disease, some 20 cases having been reported in abstract form. Previous descriptions have stressed the localized nature of skin involvement, the absence of visceral changes or Raynaud's phenomenon, an association with hypergammaglobulinaemia and eosinophilia, and a good response to corticosteroid therapy. The most conspicuous feature of this entity has been a massive thickening of the subcutaneous fascia, when an adequate (skin down to muscle) biopsy has been performed. We report another case conforming to these general features, with the exception that Raynaud's phenomenon was a prominent symptom. A critical review of the literature suggests that eosinophilic fasciitis should tentatively be regarded as a variant of scleroderma.

Adult↗

Mixed connective tissue disease--clinical and radiological aspects of 20 cases.

The clinical and radiological features of 20 cases of mixed connective tissue disease (MCTD), a newly defined disorder, are described. MCTD shares a number of abnormalities with other collagen diseases, notably diffuse systemic sclerosis and systemic lupus erythematosus. However, patients with MCTD have a specific circulating antibody to extractable nuclear antigen (ENA). Most of the cases described exhibited multi-system involvement with radiological changes in the skeleton, chest, and gastro-intestinal tract. Twelve of the 20 cases had an erosive arthritis. This finding has not been previously noted in the radiological literature.

Antibodies↗

Aspirin hepatotoxicity and disseminated intravascular coagulation.

A 17-year-old girl with a clinical diagnosis of adult-type juvenile rheumatoid arthritis developed a severe hepatotoxic reaction to 3.6 g of aspirin per day. This was associated with a microangiopathic anemia and transient congestive cardiac failure. She responded well to steroids, and when all laboratory test findings were back to normal, she was "challenged" with five divided doses of aspirin (total, 3.0 g). This produced a salicylate level of 9.1 g/dl and was associated with an immediate deterioration in liver function test findings and a return of microangiopathic blood features with elevation of fibrin split products and a prolonged prothrombin time. These changes were again reversed by promptly starting steroid therapy. This case suggests that disseminated intravascular coagulation, and its rare association with hepatotoxicity, is a potentially fatal side effect of aspirin therapy.

Adolescent↗

Characterization of DNA used to assay sera for anti-DNA antibodies; determination of the specificities of anti-DNA antibodies in SLE and non-SLE rheumatic disease states.

Commercial 14C-labeled KB cell DNA, widely used to assay sera for anti-DNA antibodies, was chromatographed on benzoylated-naphthoylated-DEAE-cellulose (BNDC) and on hydroxyapatite (HAP). On BNDC, only 25% of the 14C label eluted with 1 M NaC1 (KB fraction I) characteristic of ds-DNA. Fifty-five percent of the label eluted with 50% formamide-1 M NaC1 (KB fraction II) characteristic of ss or denatured DNA. On HAP, however, none of the 14C label eluted with 0.2 M phosphate buffer as anticipated for ss-DNA, but, rather, all of the 14C label eluted with 0.4 M phosphate, characteristic of ds-DNA. after pretreatment with S1 endonuclease of Aspergillus oryzae, which selectively digests ss regions, however, 42% of the 14C label was lost from the 0.4 M phosphate peak. These results indicated that more than half of this 14C-KB-cell DNA preparation was ds-DNA with ss regions which was undetectable by HAP chromatography. 3H-ds-DNA and circular 3H-ss-DNA prepared from T7 and phiX174 bacteriophage, respectively, were found to be chromatographically pure on both BNDC and HAP. None of 10 non-SLE sera (rheumatoid arthritis 3, mixed connective tissue disease 4, scleroderma 1, ulcerative colitis 1, and pulmonary fibrosis with chronic active hepatitis 1), previously believed to contain anti-ds-DNA antibodies on the basis of KB cell DNA testing and detectable antibodies against KB fraction 1 or T7 DNA: all of 10 KB cell DNA positive SLE sera had antibodies against both. Additionally, none of the 10 non-SLE sera had antibodies against KB cell DNA when retested with DNA that had been pretreated with S1 endonuclease. Seven of these 10, however, as well as all 10 SLE sera, had antibodies against phiX174 DNA, KB fraction II DNA and alkali-denatured T7 DNA. The data support the conclusions that 1) false positive tests for anti-ds-DNA antibodies can result from contamination of ds-DNA with ds-DNA having ss regions, and 2) non-SLE sera do not contain antibodies specific for ds-DNA at levels comparable to those found in SLE sera but rather contain high levels of antibodies reacting with ss regions or mixed DNA.

Antibodies↗

Double-blind, multi-centre parallel trial of ketoprofen and ibuprofen in the treatment of rheumatoid arthritis.

A double-blind parallel multi-centre study of 102 patients with rheumatoid arthritis (RA) was performed, comparing ibuprofen (1200-2400 mg daily) and ketoprofen (150-300 mg daily) a new non-steroidal, anti-inflammatory agent, over a three month period. Ketoprofen was well tolerated and shown to have comparable efficacy with ibuprofen. Longterm efficacy and tolerance studies are indicated.

Adult↗

Measurement of DNA antibodies.

Modifications of the standard Farr technic for assaying DNA antibodies are presented; these result in improved separation of normals from abnormals, enhanced reproducibility, and simplicity of performance. The use of 0.4 M borate buffer extends the range of the assay, while a 0.1 M buffer aids differentiation when equivocal results are obtained. Centrifugation of vials prior to counting improves the reproducibility by approximately 3%. Polyethylene glycol, at a final concentration of 6 Gm. per 100 ml., can be substituted for ammonium sulfate, with some advantages.

Antibodies↗

Nucleoprotein-coated latex particles in the serologic diagnosis of systemic lupus erythematosus. A comparative clinical and serologic study.

A commercially available test for systemic lupus erythematosus employing nucleoprotein-coated latex particles has been evaluated both clinically and serologically. The sera from all 40 subjects with active SLE had positive latex tests, while all 28 sera from healthy adults had negative latex tests. False-positive latex tests were observed in five of 13 antinuclear factor-positive patients with other chronic inflammatory diseases. Specific DNAase and RNAase digestion of the latex particles suggested the false-positive results were due to DNA moieties, other than native DNA, coating the latex particles.

Antibodies↗

Closing volumes in man immersed to the neck in water.

Closing volumes (CV), along with residual volume (RV), vital capacity (VC), along with residual volume (RV), vital capacity (VC), and expiratory reserve volume (ERV) were determined in 10 subjects in the dry and while immersed to the neck in water. Closing volumes during immersion increased 41.3% (P less than 0.001) over dry values while RV decreased 9.35% (P less than 0.001) and VC decreased 9.94% (P less than 0.001). The large decrease of 71.3% (P less than 0.001) in ERV resulted in the impingement of closing capacity (CV + RV) on the tidal volume in 9 out of 10 subjects. We interpret this to mean that airway closure occurs during tidal ventilation in immersed subjects and may result in impaired gas exchange. When tourniquets were applied to all four limbs during immersion closing volumes increased only 32.1%, but increased to 64.3% when they were removed. If engorgement of peribronchial vessels predisposes airways to collapse, a reduction of plasma volume during an extended period of immersion might lessen this possibility. In a series of long term (2.5-h) immersion experiments where moderate reductions (-10 to -7%y in plasma volume were observed, we found, however, no correlative changes in closing volume.

Adult↗

A solid-phase radioimmunoassay for the measurement of lactoferrin in human plasma: variations with age, sex, and disease.

A solid-phase radioimmunoassay is described for measuring lactoferrin levels in normal human plasma. The sensitivity of the assay was 6 ng. per milliliter with an intraassay coefficient of variation of 4 per cent and an interassay value of 9 per cent. Healthy adult males had a mean plasma level of 1.62 mug per milliliter which was significantly higher than adult females, 1.07 mug per milliliter. Postmenopausal females had levels similar to men, 1.74 mug per milliliter, while younger women had a significantly lower mean value, 0.75 mug per milliliter. Two menstruating women and 2 pregnant women had moderately elevated levels. Consistently elevated levels were found in patients with untreated or relapsing chronic myeloid leukemia--all over 12.0 mug per milliliter, while patients on marrow suppressant therapy tended to have subnormal levels. The collection of serum specimens as opposed to plasma, resulted in inconsistently elevated levels: EDTA was the anticoagulant of choice, as heparin interfered in the radioimmunoassay system.

Adult↗

Factors affecting the solubility of calcium pyrophosphate dihydrate crystals.

The solubility of triclinic calcium pyrophosphate dihydrate (CPPD) crystals was measured under varying conditions using 45Ca-labeled crystals, expressing solubility as micromoles per liter of 45Ca in solution. In a 0.1-M Tris-HC1 buffer pH 7.4, the solubility of accurately sized CPPD crystals (37-20mum) was 60muM with maximal solubility being attained after about 8 h incubation at 37degreeC. Reduction in crystal size, decrease in pH, increase in ionic strength, Mg++, citrate, and albumin all increased solubility. The most marked effects on solubility occurred when changing the calcium concentration or by enzymatic hydrolysis of inoganic pyrophosphate to orthophosphate. It was found that decreasing the ionized calcium level below 5 mg/100 ml resulted in a progressive enhancement of solubility. The observed solubility-enhancing effects of albumin could be explained solely on its calcium-binding ability and thereby, altered ionized calcium level. Diffusible calcium in synovial fluid was only 40% of the total calcium concentration, which means most joint fluids are normally near the critical concentration of 5 mg/100 ml of ionized calcium, below which solubility is enhanced. During surgery, especially parathyroidectomy, calcium levels fall, favoring dissolution of CPPD crystals. We speculate that the slight decrease in crystal size during dissolution frees them from their cartilaginous mold, resulting in a dose-dependent inflammatory reaction as they are "shed" into the joint space. Crystal shedding may be reinforced by the modest fall in joint fluid pH accompanying the inflammatory response.

Arthritis, Rheumatoid↗