Antibody deficiency associated with gold treatment: natural history and management in 22 patients.

OBJECTIVE: To perform a clinical and immunological study of patients with rheumatoid arthritis who develop subnormal serum immunoglobulins on gold treatment; to clarify the nature of the defect in antibody production and determine the natural history of this adverse reaction; to use this information to suggest guidelines for the detection, investigation, and management of this complication. METHODS: 22 patients who developed subnormal levels of one or more immunoglobulin isotypes while receiving gold treatment were recruited over a 10 year period from the practice of a single rheumatologist. Antibody production was assessed by measurement of total immunoglobulins and of specific antibody production against polysaccharide and protein antigens, with test immunisation if necessary. RESULTS: Two broad patterns of antibody deficiency were identified: (1) (n = 11) mild, affecting only one immunoglobulin isotype and with normal specific antibody production. These patients were in general able to continue gold without further deterioration in antibody production. (2) (n = 11) severe, affecting two or three immunoglobulin isotypes, with defective specific antibody production. Six patients developed significant infections and were treated with immunoglobulin. Gold was discontinued in all. Normal antibody production recovered in nine patients, and in all but one followed for more than one year. No relation was seen between duration/dose of gold and antibody deficiency. CONCLUSIONS: Gold-induced antibody deficiency may be more common than usually recognised. A spectrum of deficiency exists, with some patients developing infective complications. Antibody production should be monitored in patients on gold treatment.

Gold-induced hypogammaglobulinaemia.

Panhypogammaglobulinaemia has recently been recognized as a rare complication of gold toxicity. We report two further cases of gold-induced hypogammaglobulinaemia which also demonstrated that monitoring of immunoglobulin levels is necessary for the early detection of this condition.

Comparison of the structure of human intervertebral discs in the cervical, thoracic and lumbar regions of the spine.

Posterior and anterior heights, cross-sectional area and shape were measured for all the intervertebral discs in four spines from elderly human cadavers. Disc height was a minimum at the T4-5 level; thoracic discs were less wedge-shaped than those in the cervical and lumbar regions. Cross-sectional area increased from the cranial to caudal extremity; at the L5-S1 level the nucleus pulposus occupied a high proportion of this area. Cervical discs tended to have an elliptical cross-sectional shape, thoracic discs were more circular and lumbar discs tended to have an elliptical cross-section which was flattened or re-entrant posteriorly. This shape distribution was quantified by defining a shape index which had a maximum value of 1 for a circular cross-section. Orientations of the reinforcing fibres in the outer lamellae of the anterior annulus fibrosus were measured from 27 discs by X-ray diffraction. For these measurements, C3-4, T7-8 and L2-3 were chosen as representative of cervical, thoracic and lumbar discs. The fibre tilt, with respect to the axis of the spine, was significantly less in the cervical discs (at 65 degrees) than in the thoracic and lumbar discs (about 70 degrees). These findings are interpreted in relation to differing functional requirements and possible mechanisms of failure in the cervical, thoracic and lumbar regions of the spine in the light of current knowledge on the biomechanics of the intervertebral disc.

Pseudomonas arthritis treated with parenteral and intra-articular ceftazidime.

A 73-year-old diabetic presented with septic arthritis of the knee; Pseudomonas aeruginosa was isolated. She was successfully treated with a combination of parenteral and intra-articular ceftazidime, after failure to eradicate the organism with adequate serum levels of gentamicin and full doses of azlocillin.

Vertebral rim lesions in the dorsolumbar spine.

The frequency, distribution, and histological characteristics of vertebral rim lesions have been studied at D11 and L4 in 117 post-mortem spines in subjects aged 13-96 years. Only one lesion was found in patients less than 30 years, but thereafter the frequency increased with age. At least one rim was affected in the majority of patients greater than or equal to 50 years. They were found more frequently in the upper than the lower rim and they were also more common anteriorly than posteriorly. Lesions were associated with focal avulsion of the annulus in an otherwise healthy disc or with annular tears running into the rim. Rim lesions can be recognised radiographically by the presence of the vacuum phenomenon, vertebral rim sclerosis with or without a cup-shaped defect in the rim and osteophytes confined to one side of the disc. The histological appearances suggest a traumatic aetiology, and since bone is known to be supplied with pain sensitive nerve endings the lesions may be important in the general context of low back pain.

Secondary malignant synovitis: report of three cases and review of the literature.

Metastatic malignant deposits in joints are rare and only 16 cases have been described. The details of three further cases are presented, a girl with Hodgkin's lymphoma in a sternoclavicular joint, an elderly lady with carcinoma of the ascending colon and knee metastases and a middle-aged man, also with knee deposits, from an adenocarcinoma of lung. The clinical features together with details of synovial fluid cytology of all 19 cases are analysed.

Collagenolytic enzyme systems in human intervertebral disc: their control, mechanism, and their possible role in the initiation of biomechanical failure.

Changes in the macromolecular matrix of the intervertebral disc may predispose to biomechanical failure of the disc. Such changes would involve extracellular enzymes capable of altering the collagen and proteoglycan of the disc matrix. In this study, extracts from homogenates of both annuli fibrosi and nuclei pulposi of human lumbar discs were found to contain neutral collagenolytic, gelatinolytic, and elastinolytic enzymes in all samples assayed. The specific activity of the collagenase was higher in extracts from nuclear than from annular tissue, a difference not seen with gelatinase or elastase. The collagenase was present as both a latent and active enzyme, the other enzymes being fully active. Human intervertebral discs therefore contain enzymes capable of degrading their extracellular macromolecular matrix.

Annular tears in the dorsolumbar spine.

As part of a systemic study of the spine between D11 and S1 the distribution and severity of anterior and posterior annular tears has been assessed by charting the tears in sagittal slabs of 117 fresh specimens. No significant sex difference was seen. The number of cases with tears in multiple discs increases with age, but exceptions to this trend occurred in both young and elderly spines. Age adjusted correlation coefficients indicate that anterior and posterior tears at L4 and L5 do not predict tears at other levels. At L3 and above, significant positive correlations occur between multiple disc levels, particularly posteriorly. In patients 50o year old or more the mean anterior tear score rises sharply from L5 to peak at L2 and L1, but, in contrast, the mean posterior tear score falls from L4 to L1 in this age group. The increase in severity of anterior tears corresponds with increased mobility in the L4-L1 disc from 50-70 years. The data are compatible with 2 factors causing tears. One affects L4 and L5 in young adults and is possibly mechanical in nature; the second operates at a later age, promotes widespread disc involvement, and is primarily degenerative in nature. The increased prevalence and severity of anterior tears (and the associated increase in mobility) in the upper lumbar region in the middle aged and elderly may be a pathogenic factor in back pain for this age group.

Léri's pleonosteosis.

Seven members of one family with Léri's pleonosteosis are reported. The abnormalities found provide further clarification of the clinical features of this rare inherited disorder. There was no evidence of genetic linkage between Léri's pleonosteosis and various parameters measured. We draw attention to the importance of recognizing this and similar rare inherited dystrophies, since the prognosis is good and inappropriate therapy should be avoided.

In-vitro mobility of the lumbar spine.

As part of a systematic study of the spine between D11 and S1 the response to stress has been assessed by measuring radiologically the total and segmental mobility of 103 specimens. The method was shown to be reproducible to within 10% of total mobility. No significant sex difference was seen. Total mobility varied widely, but mean total mobility fell with age. All lumbar segments became less mobile up to the fifth decade. Between the fifth and the eighth decade the mobility of the fifth lumbar segment continued to fall, whereas other lumbar segments became more mobile. The mobility of each segment also varied widely, but the mean segmental mobility fell progressively from L5 to D11. However, this smooth pattern of movement was seen in only 16 cases, mostly adolescents and young adults. Among the remainder, in which movement was irregularly distributed, there were 7 cases (4 aged less than 30 years) in which the mobility of at least 1 segment was more than 2 standard deviations above the mean. The cause of this hypermobility was not evident radiologically. It is suggested that segments with abnormally high mobility may be at risk.

Vertebral end-plate lesions (Schmorl's nodes) in the dorsolumbar spine.

The distribution of end-plate lesions (Schmorl's nodes) and their relationship to bone density and disc degeneration have been studied in 50 post-mortem spines below D9 in subjects aged 13-96 years. Lesions were present in 76% of cases with a predominance in males. They were found more frequently in the lower than in the upper vertebral end-plate. They were also more common and more severe in the dorsolumbar (D10-L1) region than in the lower lumbar (L2-L5 region). In adults they were unrelated to age and bone density. Lesions were significantly related to disc degeneration in the D10-L1 region but not in the L2-L5 region. It is suggested that end-plate lesions arising in adolescence (or before) may predispose the dorsolumbar spine to disc degeneration in later life.

Chronic progressive external ophthalmoplegia.

The clinical features and investigative findings of 50 patients with chronic progressive external ophthalmoplegia (CPEO) were analysed. The group was found to be clinically, genetically and histologically heterogeneous. With the possible exception of patients with "ophthalmoplegia plus," namely those who in addition to muscular weakness had evidence of central and/or peripheral nervous system abnormality, there was no apparent justification for separating out from among the group patients' subgroups which were distinctive enough to be recognized as syndromes. CPEO therefore seems to represent a number of different degenerative disorders whose common denominator is ophthalmoplegia and for which there are to date no adequate criteria for further classification.

Judgment of the visual vertical and horizontal in patients with Parkinsonism.

Judgment of the visual vertical and horizontal in the upright body position was abnormal in 19 (29 percent) of 66 patients with Parkinson's disease. The magnitude of errors correlated with the degree of rigidity and of tremor in the limbs, but not with bradykinesia or other clinical features. The results suggest that the effect on visual perception of the vertical and horizontal coordinates in patients with parkinsonism is brought about by specific changes in the basal ganglia and is not, as in the case of other visual-motor tasks, determined merely by the overall severity of cerebral pathology.