Cross-sectional assessment of pain and physical function in skeletal dysplasia patients.

Short stature skeletal dysplasia (SD) patients have orthopedic and neurologic complications causing significant pain and physical disability. We conducted a large cross-sectional online survey in 361 people with short stature SD (>10 years) to describe pain prevalence, characteristics, and the relationship between pain and function. Chronic pain prevalence per Brief Pain Inventory (BPI) was 70.3%. Women reported more pain than men (73% vs 63% p = 0.04). Pain Severity Score (average of current, worst, least and average pain) averaged 3.3 ± 2, while the Pain Interference Score (with daily activities) averaged 3.4 ± 2.7 on a 10-point scale. Per Bleck scale, 20.5% had little or no functional capacity. Increasing age and decreased ambulation independently predicted chronic pain. Chronic pain is prevalent in short stature SD patients and associated with poor physical function. Further study is required to clarify the temporal relationship among pain, function and treatments.

Associations between retinal nerve fiber layer abnormalities and optic nerve examination.

OBJECTIVE: Retinal nerve fiber layer (RNFL) abnormalities detected by optical coherence tomography (OCT) are useful markers for axonal loss and visual dysfunction in multiple sclerosis (MS), but their role in routine clinical management is not well-studied. METHODS: Clinical and OCT examinations were performed on 240 patients attending a neurology clinic. Using OCT 5th percentile to define abnormal RNFL thickness, we compared eyes classified by neurologists as having optic atrophy to RNFL thickness, and afferent pupillary defect (APD) to RNFL thickness ratios of eye pairs. RESULTS: Mean RNFL thickness was less in eyes classified by neurologists as having optic atrophy (79.4 ± 21 µm; n=63) vs those without (97.0 ± 15 µm; n=417; p < 0.001, t test) and in eyes with an APD (84.1 ± 16 µm; n=44) than without an APD (95.8 ± 17 µm; n=436; p < 0.001). Physicians' diagnostic accuracy for detecting pallor in eyes with an abnormal RNFL thickness was 79% (sensitivity=0.56; specificity=0.82). Accuracy for detecting a RAPD in patients with mean RNFL ratio (affected eye to unaffected eye) <0.90 was 73% (sensitivity=0.30; specificity=0.86). Ability to detect visual pathway injury via assessment of atrophy and APD differed between neurologists. CONCLUSIONS: OCT reveals RNFL abnormality in many patients in whom eyes are not classified by neurologic examiners as having optic atrophy. Further study is needed to define the role of OCT measures in the context of examinations for optic atrophy and APD by neuroophthalmologists. OCT-measured RNFL thickness is likely to have an important future role in the clinical setting.

Weight for age charts for children with achondroplasia.

To develop accurate weight for age charts for individuals with achondroplasia. These novel weight for age, gender-specific growth curves for achondroplasia patients from birth through 16 years were constructed from a longitudinal, retrospective, single observer cohort study of 334 individuals with achondroplasia. Weight for age data from 301 subjects in this achondroplasia cohort, constituting 1,964 total weight measurements, are presented in these weight for age curves. Percentiles (5, 25, 50, 75, 95th) were estimated across the age continuum by gender, using a 1 month window (+/-0.5 months) around each time point of interest. Percentiles were smoothed using a quadratic, penalized smoother by a semi-parametric model approach. Raw weight data from the achondroplasia cohort are compared to that of average stature children presented in the current CDC growth curves, divided into 0-36 months and 2-16 years. There was overlap of birth weight between achondroplasia and average stature infants. This statistical modeling method can be applied to other anthropometric parameters collected from this achondroplasia cohort (e.g., length, BMI), other skeletal dysplasia diagnoses, and to syndromic, non-skeletal dysplasia diagnoses which may benefit from standardization of weight for age.

Relations between decision-making deficits and discriminating contingencies following brain injury.

Deficits in decision-making characterized by failures to respond adaptively to consequences that follow responding are common following brain injury. To examine decision-making about consequences, individuals with and without acquired brain injury responded under different response-reinforcer contingencies. In two control conditions, reinforcement was contingent on responding and response repetition. Results showed responding (pressing four computer keys) by both groups produced similar amounts of reinforcement (money) and highlight equal sensitivity to money as a reinforcer. In subsequent experimental conditions, reinforcement was contingent upon varying responses. Results showed both groups produced variable response patterns, but injured subjects earned less reinforcement than controls. With instructions to vary responding across trials, injured subjects earned similar amounts of reinforcement as controls. Collectively, the results suggest reductions in sensitivity to contingencies may be present following injury and function as one behavioural mechanism of maladaptive decision-making.

Acute postprandial lipaemia does not influence the in vivo activity of human platelets.

Platelet function and serum lipid studies were conducted on nine healthy male subjects before and two hours after three separate meals, two of which were rich in fat: saturated fat (SF) or polyunsaturated fat (PUF), and a third control meal which contained no fat. Platelet activity was assessed by determination of in vivo platelet aggregate formation, and plasma levels of the platelet specific proteins platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG). Serum triglyceride levels increased significantly after both fat containing meals but were unaffected by the fat free meal. Serum cholesterol levels were not affected by any of the three meals. Platelet function tests could not detect any alteration of in vivo platelet activity in terms of platelet aggregate formation or plasma concentrations of PF4 and beta-TG. These results are at variance with previously published studies that used less specific assays of platelet activity and which suggested platelet activation shortly after meals rich in SF.

Plasma concentrations of platelet-specific proteins correlated with platelet survival.

Relationships between 51Cr platelet survival and plasma concentrations of beta-thromboglobulin (betaTG) and platelet factor 4 (PF4) were analyzed in 91 studies of patients with coronary artery disease. betaTG was significantly correlated with platelet life-span, turnover, and the number of hits in the multiple hit model. PF4 was significantly correlated with life-span and turnover. The most significant relationship involving platelet-specific protein concentrations and life-span estimates was between betaTG and life-span estimated using the multiple hit model (r = -0.39, p less than 0.001). There was a high correlation between betaTG and PF4 (r = 0.62, p less than 0.001), and no improvement could be obtained by combining the measurements of the two proteins in any regression with life-span or turnover. The results indicate that the patients with the shortest platelet survival time in this group tended to have the highest plasma concentration of betaTG and PF4 and thus probably increased in vivo release of betaTG and PF4. They strengthen the claim that these platelet-specific proteins may be indicators of platelet involvement in disease.

Plasma levels of platelet factor 4 measured by radioimmunoassay.

A radioimmunoassay has been developed to measure platelet factor 4 (PF4) in biological fluids both in vitro and in vivo. The assay has been shown to be highly specific for PF4 and has a sensitivity of 0.08 ng/assay tube and 1.6 ng/ml of plasma. The preparation of plasma for the measurement of in vivo levels of PF4 requires the use of an anticoagulant containing EDTA, theophylline and prostaglandin E1, the immediate cooling of the blood and high speed or prolonged centrifugation to reduce platelet contamination. Plasma levels of PF4 are normally between 4 and 24 ng/ml with a median of 7.4 ng/ml. Plasma PF4 levels are markedly increased during cardiopulmonary bypass surgery with shortened 51Cr-labelled platelet survival times and during arterial thrombosis. However, despite similarly shortened platelet survival times, the level of PF4 is normal in immune thrombocytopenia. Elevations of plasma PF4 levels are found following surgery, acute myocardial infarction and frequently during acute infections and in inflammatory states. On the contrary, normal levels are usual in disseminated malignancy, in severe hepatic and renal disease and in chronic arterial disease. The measurement of PF4 is a useful addition to the study of platelet pathophysiology. It is apparent, however, that raised levels are by no means specific for thromboembolic disease and similarly platelet destruction is not invariably associated with abnormally increased plasma PF4 levels.

Studies on the chemistry of human platelet factor 4.

The chemical characteristics of several PF4 preparations have been examined by gel electrophoresis, amino acid analysis and NH2-terminal amino acid sequence determination. Preparations of PF4 from gel filtration and from affinity chromatography appeared identical. A single NH2-terminal sequence was determined as follows: NH2-Glu-Ala-Glu-Glu-Asp-Gly-Asp-Leu-Gin-SCMCys-Leu-SCMCys-Val-Lys-Thr-Thr-Ser-Gln-Val-Arg-. The molecular weight of the PF4 subunits, which seem to be identical, was 7,100 based on the recovery of NH2-terminal glutamic acid.

Platelet density and size: the interpretation of heterogeneity.

Platelets have been separated according to buoyant density using a colloidal silica-polyvinylpyrrolidone system and subjected to electronic sizing. All density populations were found to be heterogeneous in size, the most dense platelets ranging from less than 3 fl to greater than 21 fl in both man and rat. Light platelet fractions contained no platelets greater than 13 fl in either species. Cohort labeling with [75Se]selenomethionine showed no indication of significant change in platelet buoyant density with ageing; greater specific activity found in young, dense platelets appears to be related to increased protein synthetic activity shown in vitro and likely to occur also in their precursor megakaryocytes. It is postulated that dense, intermediate and light platelets are released synchronously by the three different ploidy classes of megakaryocyte, that varying density indicates differing structural characteristics and presumably differences in function. The present findings do not deny the possibility that platelets decrease in size with ageing but if such occurs, it is not associated with a significant change in platelet buoyant density.