The knee joint in diastrophic dysplasia. A clinical and radiological study.

We examined clinically and radiologically the knees of 46 patients (27 females and 19 males) with diastrophic dysplasia. The age of the patients varied from newborn to 38 years. A total of 18 patients was followed during their growth until adolescence. The knees of two legally aborted fetuses appeared on examination to be macroscopically normal and congruous. Excessive valgus deformity of the tibiofemoral weight-bearing angle with a mean of 14 degrees was noted in infancy. Most of the patients had marked instability of the knees. The range of movement of the knee began to decrease before the age of five years. There were signs of early degeneration and deformation of the bony epiphyses before the age of six years. The patellofemoral joint was abnormal from an early age. A marked patella infera, often associated with a lateral position of the patella with bony fragmentation, was noted. The knee in diastrophic dysplasia is basically unstable, showing early deformation of the subchondral bone and degeneration of the joint.

Health-related quality of life in patients with diastrophic dysplasia.

Diastrophic dysplasia (DD), a congenital skeletal dysplasia, is characterized by short, disproportionate stature, multiple severe spinal and joint deformities, and normal mental status. The health-related quality of life (HRQOL) of patients with DD was measured by a standardized fifteen-dimensional (15D) method, that includes a questionnaire and a valuation task. Eighteen patients (5 males and 13 females) with a mean age of 23 years (range 17-31 years), representing half of the Finnish patients with DD in this age group, completed the questionnaire and the valuation task. The data obtained were compared with those of 273 age- and sex-matched controls. A 15D profile was drawn, and the average importance weight of each dimension and the average within-dimension level values were calculated for both groups. The average 15D score, describing the overall HRQOL, was derived for both groups using the evaluations of each group. The health profiles of the groups differed significantly in several dimensions. When the health levels within the dimensions were concerned, the controls rated all values deviating from "normal" lower than did the patients. The average 15D scores of the patients with DD were significantly lower than those of the controls. The 15D scores were higher in both groups when the evaluations of the patients with DD were used. The study showed that, although the overall HRQOL of the patients with DD was inferior to that of the controls, the patients showed greater adaptability to deviations in health status than did the controls.

Development of the hip in diastrophic dysplasia.

We examined 50 patients with diastrophic dysplasia both clinically and radiologically. Two legally aborted fetuses were dissected. The mean age of the patients was 16.2 years (newborn to 38) and the mean follow-up was 11.4 years (3 months to 34 years). The fetal hips and MRI of newborn infants showed congruity and no significant joint deformity. Flexion contracture of the hip became evident later in 93% and was progressive. The radiological appearance of the proximal femoral ossific nuclei was delayed and in 17% of males and 28% of females the ossific nuclei had not appeared by the age of 12 years. Radiological measurements differed considerably from reference values and were related to the rapid and progressive restriction of rotational movement and the increase in flexion contracture. The typical findings were flattening and inferomedial bulking of the femoral head and a double-hump deformation. The changes in the hip led to secondary osteoarthritis before early middle age. We describe the clinical and radiological measurements which define the early degeneration of the joint.

Ultrasonography of the patellofemoral joint in diastrophic dysplasia.

Plain radiographs do not provide adequate information in diastrophic dysplasia (DD) because of abnormal ossification and severe deformation of the knee joint. Radiographically, the lateral femoral condyle is hypoplastic, and the position of patella is difficult to define. In clinical examination, the patella is inferior and lateral. In this study, the anatomy of the patellofemoral joint in DD is described using ultrasound. Both knees of 13 patients with DD were examined. The alignment of patella, the angle of femoral sulcus, and the size of both femoral condyles were measured. Student's paired t test with two-tailed significance probability was applied for differences in mean values, and their 95% confidence limits were computed. The femoral sulcus angle averaged 129 degrees and was deeper than that (142 degrees) in normal knees. The lateral femoral condyle was smaller than the medial condyle. The patella was aligned lateral to the bottom of femoral sulcus. In 10 degrees knee flexion, the patella remained laterally in the sulcus with no true patellar dislocation. Vertical position of the patella averaged 2.9 mm distal to the femorotibial joint. The study showed that, in patients with DD, the anatomic complex of the femoral condyles and patella deviates laterally, and the patellofemoral joint is deformed with a hypoplastic lateral condyle, a deep femoral groove, and a distally aligned patella.

Neutrophil migration in vivo and in vitro in healthy neutropenic subjects.

Migration of polymorphonuclear leukocytes (PMN) was studied in six healthy subjects with neutropenia (peripheral blood neutrophil count less than or equal to 1.5 X 10(9)/1). Determined as migration differentials, chemotactic and chemokinetic responsiveness tended to be higher in the neutropenic group. Despite this slight tendency to increased responsiveness in vitro, migration in vivo proceeded more slowly in the neutropenic group than in the control group: at 12 hours the leukocyte counts in the skin chamber media were significantly lower, whereas at 24 hours they were nearly normal. Our results show that PMN migration in healthy neutropenic subjects is different from that in healthy non-neutropenic subjects. These differences should be taken into account in the evaluation of the role of aberrant PMN migration in the development of infectious episodes in a neutropenic patient.

Polymorphonuclear leucocyte function and previous yersinia arthritis: correlation of enhanced superoxide production with late manifestations.

Polymorphonuclear leucocyte (PMN) functions (migration in vitro, chemiluminescence, O-2 production, and aggregation) were studied in 32 patients with previous yersinia arthritis (YA). PMNs of 11 HLA-B27 positive patients who had chronic or recurrent inflammatory symptoms showed O-2 production significantly higher than that of PMNs of 11 HLA-B27 positive patients without late manifestations. Also, PMNs of both HLA-B27 positive and negative patients tended to show chemotactic and chemokinetic migration rates higher than those of control cells of healthy HLA-B27 negative subjects. These functional aberrations may play a part in the development of the patients' inflammatory symptoms.

Bacterial-lipopolysaccharide-induced release of lactoferrin from human polymorphonuclear leukocytes: role of monocyte-derived tumor necrosis factor alpha.

We have examined the role played by human peripheral blood monocytes in mediating responses of human polymorphonuclear leukocytes (PMN) to bacterial lipopolysaccharide (LPS) in vitro. When incubated with Salmonella typhimurium LPS at 37 degrees C, human PMN suspended in serum-free buffer released the specific granule constituent lactoferrin into the surrounding medium. Release of lactoferrin from PMN varied with the concentration of LPS (1 to 1,000 ng/ml) as well as with the duration of incubation (2 to 60 min) and was not accompanied by significant release of the cytoplasmic enzyme lactate dehydrogenase. LPS-induced release of lactoferrin from PMN was augmented significantly when cell suspensions were supplemented with additional monocytes and lymphocytes. Only monocytes, however, secreted significant amounts of lactoferrin-releasing activity (in a time- and concentration-dependent manner) when incubated separately with LPS. Lactoferrin-releasing activity was heat (80 degrees C for 15 min) labile, eluted after chromatography on Sephadex G-100 with an apparent molecular weight of approximately 60,000, and was inhibited by antibodies to tumor necrosis factor alpha. Thus, LPS-induced noncytotoxic release of lactoferrin from human PMN suspended in serum-free buffer is mediated, at least in part, by tumor necrosis factor alpha derived from contaminating monocytes.

Polymorphonuclear leucocyte function and previous yersinia arthritis: enhanced chemokinetic migration and oxygen radical production correlate with the severity of the acute disease.

Polymorphonuclear leucocyte (PMN) functions (migration in vitro, chemiluminescence, O-2 production, binding of chemotactic peptide, and aggregation) were studied in HLA-B27 positive patients with previous yersinia arthritis (YA). PMNs of patients whose disease had been severe showed chemokinetic and chemiluminescence responses significantly higher than the PMNs of those with a mild disease. The results support the view that enhanced PMN function contributes to inflammatory symptoms in patients with YA.

Neutrophil migration in vivo: analysis of a skin window technique.

The applicability of a skin chamber technique for the quantitation of neutrophil migration in vivo was studied in healthy subjects. Skin lesions were generated on lower abdominal skin by separating epidermis from dermis by suction. In 23 subjects the mean chamber cell count at 24 h was 20.9 X 10(6)/cm2 of skin lesion area, and 97.5% of the cells were neutrophils. An analysis of the variance in up to 8 parallel chambers in 10 subjects supported the use of 4 simultaneous replicates. Reproducibility in consecutive experiments was studied by testing 9 persons twice; the results were found to agree closely. Kinetic studies were performed in 15 subjects. The method is useful for the in vivo study of diseases and medications thought to affect leukocyte function.

Enhanced neutrophil migration in vivo HLA B27 positive subjects.

Chemotaxis of polymorphonuclear leucocytes in vivo was studied in patients with previous yersinia arthritis and in healthy subjects with or without HLA B27 by means of a skin chamber technique. Irrespective of previous arthritis the number of neutrophils in the chamber media was significantly higher in HLA B27 positive subjects than in those without HLA B27. The amounts of prostaglandins E2, F2 alpha, and 6-keto-F1 alpha in the chamber media correlated positively with the corresponding cell counts. The present results give credence to the view that the hyperreactive neutrophils and the vasodilatory prostaglandins produced by them can together trigger a vicious circle which results in increased inflammatory symptoms in patients with yersinia arthritis who have HLA B27 as compared with those who lack this antigen.

Exaggerated inflammatory responsiveness plays a part in the pathogenesis of HLA-B27 linked diseases--hypothesis.

Ankylosing spondylitis, acute anterior uveitis and reactive arthritides, including enteroarthritis and uroarthritis , are all associated with the human leucocyte antigen (HLA) B27. The pathogenesis of these diseases is not known, but it may involve inflammatory responsiveness of the host. In an acute inflammatory reaction, neutrophils are considered to cause tissue injury by both liberating lysosomal enzymes and generating toxic oxygen-derived free radicals. Furthermore, they may regulate both capillary permeability and the rate of vasodilatation at the site of inflammation. Evidence has accumulated that neutrophil responses to a phlogistic stimulus are enhanced in HLA-27 positive subjects. We suggest that hyperreactive neutrophils trigger a vicious circle of inflammation and render the subjects susceptible to exaggerated tissue injury.